Case Of Plasmablastic Lymphoma Research Articles

Clinicopathological and genetic landscape of plasmablastic lymphoma in Taiwan

Plasmablastic lymphoma (PBL) is an aggressive large B-cell lymphoma with a terminal B-cell differentiation phenotype and is frequently associated with immunodeficiency. We aimed to investigate the clinicopathological and immunophenotypic features, genetic alterations, and mutational landscape of PBL in Taiwan. We retrospectively recruited 26 cases. Five (5/18; 28%) patients were HIV-positive and 21 (81%) presented extranodally. There were two morphological groups: one with purely monomorphic large cells (85%) and the other comprising large cells admixed with plasmacytic cells (15%). Phenotypically, the tumors expressed MYC (8/10; 80%), CD138 (20/26; 77%), and MUM1 (20/20; 100%), but not CD20 (n = 26; 0%). Fourteen (54%) cases were positive for EBV by in situ hybridization; the EBV-positive cases were more frequently HIV infected (p = 0.036), with extranodal presentation (p = 0.012) and CD79a expression (p = 0.012), but less frequent light chain restriction (p = 0.029). Using fluorescence in situ hybridization, we identified 13q14 deletion, MYC rearrangement, and CCND1 rearrangement in 74%, 30%, and 5% cases, respectively, without any cases having rearranged BCL6 or IGH::FGFR3 fusion. In the 15 cases with adequate tissue for whole exome sequencing, the most frequent recurrent mutations were STAT3 (40%), NRAS (27%), and KRAS (20%). In conclusion, most PBL cases in Taiwan were HIV-unrelated. Around half of the cases were positive for EBV, with distinct clinicopathological features. Deletion of chromosome 13q14 was frequent. The PBL cases in Taiwan showed recurrent mutations involving JAK-STAT, RAS-MAPK, epigenetic regulation, and NOTCH signaling pathways, findings similar to that from the West.

Plasmablastic Lymphoma: The 'Rare' Frequency Among Immunocompromised Patients

Limfoproliferations associated with HIV infection/AIDS are rare conditions, with an incidence of malignant lymphomas of approximately 10% among the 25-40% malignancies that can occur in these immunosuppressed patients (1). Plasmablastic lymphoma (PBL), with an incidence of only 2% (out of the total lymphomas), is a borderline form (morphologically and immunophenotypically) between lymphoma and myeloma, defined by its high aggressiveness and unfavorable prognosis (2). Objectives: identifying the clinical, histopathological, and biological characteristics of PBL that require a differential diagnosis within other malignant hematological conditions associated with HIV infection. Materials and Methods: We present three comparative cases of PBL that were observed at the Colțea Hematology Clinic in a short time window (4 months). All patients were diagnosed with PBL in the context of HIV/AIDS infection, with an average age of approximately 41 years, predominantly male (66.6%), and with a symptomatology onset characteristic of immunocompromised individuals (manifesting at the oral, lymph node, and cutaneous levels), but with specific aspects related to associated comorbidities (e.g., psychiatric pathology, dilated cardiomyopathy), risk behaviors (e.g., intravenous drug use for 20 years), and infectious/ non-infectious complications, which influenced the patients' evolution. Conclusions: Plasmablastic lymphoma still represents a highly aggressive condition with an unfavorable prognosis, possibly having a higher clinical incidence than that described in the literature and requiring a adequate multidisciplinary approach.

Genetic Subtyping Using Whole Exome Sequencing across Large B Cell Lymphoma Entities in a Series of 109 DLBCL and Plasmablastic Lymphoma Cases

Background: Diffuse Large B Cell Lymphomas are still a significantly heterogeneous disease with few molecularly defined entities. Recently genomic based algorithms have been proposed for DBCL NOS disease classification, including the Lymphgen tool 1. Other large B cell lymphoma entities, including High Grade BCL Dual Hit or plasmablastic lymphoma remain poorly characterized according to this molecular based clustering methods. Here we sought to apply this tool for disease classification in a series of 109 large B cell lymphoma cases derived from GELTAMO clinical trials (NCT01848132 and NCT2015-005390-21) and retrospective multicentric series to confirm its application across different large B cell lymphoma entities. Methods: We retrieved FFPE and liquid biopsy diagnostic samples from 109 cases and performed histopathological confirmation, FISH testing and whole exome sequencing (Agilent Sureselect v6) by NGS. Sequencing data and available fusion data for BCL2 and BCL6 were used to classify the cases according to Lymphgen (https://llmpp.nih.gov/lymphgen). Results: 109 cases were classified as different large B cell lymphoma entities, including 31 DLBCL NOS GCB type, 8 HGBCL/DLBCL DH/NOS, 41 DLBCL NOS non-GCB type, 22 plasmablastic lymphoma, 3 THRLBCL, 1 PMBL, 2 DLBCL NOS and 1 3B Follicular Lymphoma. After WES median Tumor Mutation Burden was 972. Overall genetic classification by Lymphgen was obtained in 53 cases (49%) with the remaining 56 cases considered unclassified (molecular subtype other/NOS). Of the genetically identified cases, 18 were classified as ST2 (33%), 15 were considered EZB (28%), 5 BN2 (10%) and 3 MCD (5%). Interestingly 12 (22%, overall, 11%) were genetically composite, including 8, ST2/EZB; 1, ST2/BN2; 1, ST2/MCD and 2 ST2/EZB/MCD. According to histopathological subtype 17 GCB type DLBCL were classified as EZB (8, 47%), ST2 (5, 30%) and BN2 (1, 6%). 3 cases (17%) were genetically composite. 6 out of 8 cases of HGBCL/DLBCL DH/NOS were classified as either EZB (2), ST2 (2) or composite EZB/ST2 (2). 19 non-GCB type DLBCL were classified as ST2 (5, 26%), BN2 (4, 21 %), EZB (3, 16 %) and MCD (3, 16%). 4 cases were genetically composite (21%). Interestingly, plasmablastic lymphomas showed ST2 genetic features, found in 5 out of 22 (23%) and composite ST2/EZB in 2 cases. Genes overrepresented in the ST2 cluster include TET2, PRRC2C, STAT3,DOCK8 and CLTC. Plasmablastic Lymphomas classified as other showed recurrent mutations in PRRC2C, PABPC1, TRRAP, PRKCB, EP300 and TP53. Conclusions: ST2 and EZB genetic groups stand as the most frequent genetic subtypes of DLBCL NOS. While ST2 is found in either GCB and non-GCB subtypes, EZB is found preferentially in cases with the GCB phenotype, including GCB type DLBCL and HGBCL/DLBCL DH. In comparison with already published series we found a relatively higher prevalence of the ST2 genetic subtype among DLBCL NOS. MCD and BN2 genetic subtypes are restricted to the non-GCB subtype, but its prevalence is relatively low. Importantly, a significant fraction of cases (~50%) is still genetically unclassified (molecular subtype NOS) using WES and FISH-derived fusion data. Proper identification of the A53 cluster and relevant dysregulated pathways in the molecular NOS group require more research. Specific large B cell lymphoma entities such as plasmablastic lymphoma show features of ST2 genetic subtype in a significant fraction of tumors. These features include JAK/STAT3 pathway activation related genes and fit well with already published data 2,3. In addition, recurrent mutations in TET2, involved in epigenetic regulation of gene expression and TRRAP, target of C-MYC transcriptional activation, were enriched in this molecular subtype of plasmablastic lymphoma. Importantly ~70% remained unclassified. Mutations in this group are recurrently found in PRRC2C as well as PABPC1, both involved in VEGFA-VEGFR2 signaling. In summary, DLBCL NOS molecular subtyping supplies exact molecular classification in ~50% of our cohort. ST2 and EZB subtypes constitute ~60% of the cases with a fraction of ~15% of composite ST2/EZB. Application of the molecular classifier to plasmablastic lymphomas shows intraspecific genetic diversity and points toward dysregulation of JAK/STAT, MAPK/Erk and VEGFA-VEGFR2 signaling as well as MYC transcriptional activation. REFERENCES 1. PMID: 32289277 2. PMID: 33225311 3. PMID: 32273478

B-Cell Maturation Antigen (BCMA) Expression and Clinical Features of Plasmablastic Lymphoma (PBL)

Introduction: Plasmablastic lymphoma (PBL) is a rare and aggressive subtype of large B-cell lymphoma with plasmacytic differentiation. Although limited-stage (LS) PBL has a favorable outcome, extensive-stage (ES) PBL has a poor prognosis, with a median survival of 12-18 months. Patients with relapsed/refractory (r/r) PBL have limited treatment options and most die from the disease. B cell maturation antigen (BCMA) - directed cellular and immunotherapies are highly effective in MM. The data on BCMA expression in PBL is limited. Literature review identified one report including 7 PBL cases all of which expressed BCMA. We studied all patients with a diagnosis of PBL who presented to Moffitt Cancer Center in Florida, USA from Jan. 2006 to Apr. 2023, and retrospectively performed BCMA immunohistochemistry (IHC) staining on the available archived FFPE biopsy samples. Methods: Progression-free survival (PFS) was calculated as time from disease progression or last follow up to treatment start date. Overall survival (OS) was calculated as time from death or last follow up to date of PBL diagnosis. Association of BCMA expression with PFS or OS was evaluated using logrank test, with continuous variables converted to categorical by classifying as above or below median. All analyses were done using SAS 9.2. Results: A total of 32 PBL patients were identified. The median age was 59 years (range 31-83 years); 21 (65.6%) had stage III/IV (ES); 9 patients (28.1%) were HIV positive; and 57.1% of evaluated cases were EBV positive by EBER. Treatment data was available for 30 patients. The most common frontline therapies were EPOCH and CHOP with or without rituximab; four patients received bortezomib combined with EPOCH; 7 patients (23.3%) received autoSCT in 1 st remission (Table 1). Median follow-up was 77.6 months calculated using the reverse Kaplan-Meier method. Consistent with previous reports, patients with ES PBL had worse outcome than those with LS PBL, with 3-year OS rates of 24% and 100%, respectively, p=0.01 (Table 1). Among the 20 patients with ES PBL and known treatment responses, 11 did not achieve CR after frontline therapy. Ten of these 11 patients died due to disease progression, 9 within 2 years and 1 within 3 years. Two patients received CD19 CAR-T after multiple lines of therapy. Both died within 30 days, one from disease progression and the other from multiple treatment complications. Out of the 18 cases with tissue available for IHC study, 17 (94.4%) had positive BCMA expression (Figure 1). The median percentage of BCMA+ cells was 75% (Table 1). Eleven (61.1%) cases had intermediate to strong BCMA staining. Neither BCMA+ cell percentage nor BCMA expression level was associated with disease stage, response rate, PFS, or OS (p>0.10 for all tests). Discussion: In our study the majority of our PBL cases tested positive for BCMA, and the percentage of BCMA+ cells seemed comparable to MM cases.To our knowledge, this is the largest and the first report that systemically evaluated BCMA expression in PBL. Our results provide evidence to explore BCMA as a potential target in PBL. Currently two anti-BCMA CAR-T products and an anti-BCMA/CD3 bispecific T-cell engager have been approved for r/r MM. A BCMA-targeting antibody-drug conjugate (ADC) Belantamab mafodotin-blmf was initially granted accelerated approval by FDA for r/r MM but was later voluntarily withdrawn from the market. Given the expression of BCMA in PBL and the lack of effective treatment of r/r PBL, these patients could be considered in trials evaluating the BCMA-targeting therapies. In fact, in a case report recently published, one patient with refractory PBL achieved CR after one infusion of BCMA CAR-T and remained in CR after 14 months. Ten of our 11 ES patients who did not achieve CR after frontline chemotherapy died from the disease, emphasizing the importance of clinical trials for this condition. We did not find an association of BCMA expression with clinical outcomes as oppose of MM, in which higher BCMA expression was associated with shorter PFS and OS. The lack of association in our study may be due to the small sample size, or, it may reflect a difference in biological role of BCMA in PBL from MM. Our results will need to be corroborated with other series to confirm our findings. Translational studies need to evaluate the dynamics of BCMA protein expression on PBL cell membrane and the activity of BCMA-targeting agents in vitro and in animal models of PBL.

Molecular characterization and clonal evolution in Richter transformation: Insights from a case of plasmablastic lymphoma (RT-PBL) arising from chronic lymphocytic leukaemia (CLL) and review of the literature.

Molecular characterization and clonal evolution in Richter transformation: Insights from a case of plasmablastic lymphoma (RT-PBL) arising from chronic lymphocytic leukaemia (CLL) and review of the literature.

Cytological features of oral malignant lymphoma in scraping liquid-based cytology: Cases of plasmablastic lymphoma and anaplastic lymphoma kinase-positive anaplastic large cell lymphoma

The main purpose of cytological examination in the oral region is to screen for squamous cell carcinoma or intraepithelial neoplasms; thus, the background tends to be considered a deterrent for microscopy. From this perspective, liquid-based cytology (LBC) is favorable for preparing clear samples with few backgrounds. However, background hemocytes are sometimes of critical importance in the diagnosis. We report two cases of oral malignant lymphoma, plasmablastic lymphoma, and anaplastic large cell lymphoma in which careful observation of the background in scraping LBC sample contributed to the early diagnosis. Atypical lymphoid cells were observed only in a very small part of the LBC samples from the presented patients; however, cytological findings, such as large lymphoid cells with outstanding nucleoli, large mitotic cells, or intermediate-to-large lymphoid cells with pleomorphic nuclei were sufficient for obtaining a cytological diagnosis of malignant lymphoma. Although the number and cell size of leukocytes in LBC with Papanicolaou staining were significantly different from those in air-dried conventional smears with Romanovsky staining, which are commonly preferred for the discrimination of hemocytes, the corresponding cytological features could be observed. Therefore, attention should be paid to the background as well as squamous epithelium to prepare for such unexpected cases. The LBC examination with Papanicolaou staining alone can suggest the possibility of malignant lymphoma.

ORAL DIAGNOSIS OF PLASMABLASTIC LYMPHOMA: A REPORT OF TWO CASES

Plasmablastic lymphoma (PBL) is a rare and aggressive B-cell malignancy that usually has a poor prognosis. Oral manifestations in the PBL are second in frequency, and the most common location is the palate or gingiva. Our study presents 2 cases of PBL with palate manifestation. A 51-year-old, HIV negative man presented an asymptomatic lesion and a female, HIV positive and smoker, presented a symptomatic growth. Clinically, both lesions exhibited a nodule with an ulcerated surface, undefined limits, and a purplish color. An incisional biopsy was performed, with a histopathological diagnosis compatible with plasma cell neoplasm. Immunohistochemical analysis confirmed the diagnosis. They were referred to HematOncology team for treatment, which consisted in DA-EPOCH (dose adjusted etoposide, prednisolone, vincristine, cyclophosphamide, and doxorubicin) combined with MADIT (combination of methotrexate, cytosine arabinoside, and dexamethasone intrathecal). The male patient is receiving chemotherapy and the female patient died during the 3rd cycle of chemotherapy during COVID-19. Plasmablastic lymphoma (PBL) is a rare and aggressive B-cell malignancy that usually has a poor prognosis. Oral manifestations in the PBL are second in frequency, and the most common location is the palate or gingiva. Our study presents 2 cases of PBL with palate manifestation. A 51-year-old, HIV negative man presented an asymptomatic lesion and a female, HIV positive and smoker, presented a symptomatic growth. Clinically, both lesions exhibited a nodule with an ulcerated surface, undefined limits, and a purplish color. An incisional biopsy was performed, with a histopathological diagnosis compatible with plasma cell neoplasm. Immunohistochemical analysis confirmed the diagnosis. They were referred to HematOncology team for treatment, which consisted in DA-EPOCH (dose adjusted etoposide, prednisolone, vincristine, cyclophosphamide, and doxorubicin) combined with MADIT (combination of methotrexate, cytosine arabinoside, and dexamethasone intrathecal). The male patient is receiving chemotherapy and the female patient died during the 3rd cycle of chemotherapy during COVID-19.

Тhree similar cases of plasmablastic lymphoma in HIV-infected persons

X-ray morphological and clinical picture with three cases of plasmablastic lymphoma among HIV-infected with a distinctive localization of neoplastic process in the head-neck area is observed. Plasmablastic lymphoma is quite a rare pathology, characterized by extremely aggressive course of the disease and multiplicity of damage. Due to this fact, it represents a medical issue, as late diagnosis of the tumor leads to a high frequency of relapse and, accordingly, to poor prognosis.

P1233: PRIMARY REFRACTORY PLASMABLASTIC LYMPHOMA: A PRECISION ONCOLOGY APPROACH

Background: The comprehensive implementation of standardized multidisciplinary molecular tumor boards (MTB) and synchronous advancements in genomic profiling diversified the spectrum of treatment strategies in cancer patients, predominantly focusing on those with solid tumors. However, hematologic malignancies remain underrepresented in MTBs. Aims: The current study aimed to assess the potential of precision oncology for primary refractory plasmablastic lymphoma (PBL), a highly lethal blood cancer. Methods: We re-evaluated previously published whole exome sequencing (WES) data of 14 primary refractory PBL cases from initial diagnosis. For this proof-of-concept study, the institutional MTB pipeline (University Cancer Center Schleswig-Holstein: UCCSH) which is certified for routine clinical diagnostics has been conducted for the individual annotation of mutations aiming to virtually recommend molecularly stratified treatment strategies. Evidence levels for MTB-recommendations were defined in accordance with the NCT/DKTK MASTER program. Results: Median age was 76.5 years (range 56-91) and 78.6% patients were male. The composition of given cytoreductive regimens was heterogenous and the overall prognosis was dismal. The standard turn-around time for the MTB pipeline after sampling was 21 days. Potential recommendations on a molecular stratified treatment option with a NCT/DKTK evidence level of at least m2A were detected for each PBL case. Based on immunohistochemical assessment (CD19, CD30, CD38 and CD79B), data-base research revealed targeted treatment recommendations in 11/14 (78.6%) cases. Genetic alterations were classified in accordance with biomarker/treatment baskets proposed by Horak et al. According to baskets, we identified tyrosine kinases (TK; n=7), PI3K-MTOR-AKT pathway (PAM; n=3), cell cycle alterations (CC; n=2), RAF-MEK-ERK cascade (REM; n=2) and others (OTH; n=7) for targeted treatment recommendations. Moreover, immunotherapeutic approaches seemed feasible in 6 PBL cases due to the predominant affection of DNA-damage repair genes. Each recommended drug was either approved by the FDA and/or EMA or at least designated for FDA fast track development. Summary/Conclusion: The presented proof-of-concept study demonstrates the applicability of precision oncology approaches in PBL patients. Due to the aggressive course of the disease, such patients are in urgent medical need for personalized treatment approaches instead of conventional chemotherapeutic options and should be considered for MTB inclusion at the earliest time.

Clinicopathologic and Molecular Characterization of Epstein-Barr Virus-positive Plasmacytoma.

Epstein-Barr virus (EBV)-positive plasmacytoma is a rare plasma cell neoplasm. It remains unclear whether EBV-positive plasmacytoma represents a distinct entity or a variant of plasmacytoma. It shares morphologic features with plasmablastic lymphoma (PBL) and may cause diagnostic uncertainty. To better understand EBV-positive plasmacytoma and explore diagnostic criteria, this study describes 19 cases of EBV-positive plasmacytoma, compared with 27 cases of EBV-negative plasmacytoma and 48 cases of EBV-positive PBL. We reviewed the clinicopathologic findings and performed immunohistochemistry, in situ hybridization for EBV, fluorescence in situ hybridization for MYC , and next-generation sequencing. We found that 63.2% of patients with EBV-positive plasmacytoma were immunocompromised. Anaplastic features were observed in 7/19 cases. MYC rearrangement was found in 25.0% of them, and extra copies of MYC in 81.3%. EBV-positive and EBV-negative plasmacytomas possessed similar clinicopathologic features, except more frequent cytologic atypia, bone involvement and MYC aberrations in the former group. The survival rate of patients with EBV-positive plasmacytoma was comparable to that of patients with EBV-negative plasmacytoma. In comparison to PBL, EBV-positive plasmacytoma is less commonly associated with a "starry-sky" appearance, necrosis, absence of light chain expression, and a high Ki67 index (>75%). The most recurrently mutated genes/signaling pathways in EBV-positive plasmacytoma are epigenetic regulators, MAPK pathway, and DNA damage response, while the most frequently reported mutations in PBL are not observed. Collectively, EBV-positive plasmacytoma should be regarded as a biological variant of plasmacytoma. Thorough morphologic examination remains the cornerstone for distinguishing EBV-positive plasmacytoma and PBL, and molecular studies can be a valuable complementary tool.

Epidemiological characteristics and cause-specific survival analysis of plasmablastic lymphoma (PBL) using the SEER database.

e19546 Background: Plasmablastic lymphoma (PBL), a variant of diffuse large B-cell lymphoma, is a rare and aggressive malignancy. Minimal guidelines exist for its diagnosis and standard of care. Hence, we studied the epidemiological characteristics and survival variables of PBL patients by using the SEER 20 database. Methods: A total of 229 cases of PBL (WHO ICD-O-3 codes 9735/3) were identified between 2000 and 2015, after excluding 66 cases with unknown survival time or no microscopic confirmation. The epidemiological characteristics and the survival variables included were age, gender, ethnicity, Ann Arbor stage, B-symptoms, and site. The overall 5-year survival (OS), cause-specific 5-year survival (CSS), and cause-specific survival plots across different strata were plotted using the Kaplan Meier Method. The analysis was done using the Cox proportional hazard regression model (p < 0.05). Results: The incidence of PBL was 0.03 per 100,000 cases. It was more common in adults less than 60 years (61.57%), males (79.04%), and White ethnicity (72.49 %). There were more cases of patients with advanced Ann Arbor stages (3 or 4) PBL (52.84%), although some patients (5.68%) had unknown staging. There were 55.02% of extranodal cases, and 28.38% of patients had B-symptoms. The OS was 36.55%, and the CSS was 46.5%. CSS did not differ significantly based on age, race, or gender. However, the absence of B-symptoms was associated with better CSS (HR: 0.654, 95% CI: 0.455-0.941, p: 0.022). Nodal involvement (HR: 1.553, 95% CI: 1.135-2.124, p: 0.006) and advanced stages 3 or 4 (HR: 1.414, 95% CI: 1.018-1.962, p: 0.038) were also linked to a poor CSS. Conclusions: PBL patients with a primary nodal involvement and advanced staging (3 or 4) had poor CSS, and the absence of B-symptoms was associated with a better outcome. Age, gender, and ethnicity had no discernible effects on survival. We did not include therapeutic options in our study, and hence, further studies analyzing the impact of treatment options on PBL survival can be conducted.[Table: see text]

Clinical Outcome and Prognostic Factors of Patients with Richter's Syndrome: Retrospective Multicenter Study of the Spanish Chronic Lymphocytic Leukemia (CLL) Study Group (GELLC)

Richter syndrome (RS), the development of diffuse large B-cell lymphoma (DLBCL) in the context of CLL, is an uncommon complication with a dismal prognosis. Currently, data on biological and clinical features, and factors predicting the outcome of patients are scarce, and there is still no consensus on the best therapeutic approach for these patients (pts). The aim of this study was to analyze the presenting characteristics, treatment outcomes, and factors predicting for survival in a series of pts with RS from a large population-based cohort of the Spanish CLL Study Group (GELLC).Pts diagnosed with RS during 1988 - 2017 were retrospectively identified in eleven centers of the GELLC group. Only cases with confirmed biopsy-proven RS during follow-up were included. Clinical-biological features at diagnosis of RS, including cytogenetics, clonal relation with the pre-existing CLL, Epstein-Barr virus (EBV) status detected by in situ hybridization, cell of origin (COO) analyzed by immunohistochemistry, International Prognostic Index score (IPI) and the RS score (Tsimberidou AM et al, J Clin Oncol, 2006), as well as treatment and outcomes, were analyzed.One hundred and twenty-three pts with transformation of CLL to high-grade lymphoma were identified, including 108 classical DLBCL RS, 14 pts with Hodgkin lymphoma (HL), and one case of plasmablastic lymphoma. Median age of the whole series was 66 years (range, 31 to 92 years), and 64% were men. For the DLBCL RS, median time from the diagnosis of CLL to RS development was of 4.7 years (range, 0-24.8 years, with 9 simultaneous diagnosis of CLL and RS), and the median number of prior therapies for CLL/SLL was 1 (range, 0-7). The main clinical characteristics of the pts are shown in table 1. EBV was detected in 12/36 (33%) cases with classical RS and in 9/11 (82%) of patients with HL variant. According to COO the majority of RS tested (20 of 24, 83%) had a non-germinal center phenotype, whereas 19/23 (83%) cases were clonally related to the preceding CLL. Twelve out of 43 pts had 17p deletion or mutation of TP53 in the CLL clone at the time of RS diagnosis.Among the 108 patients with DLBCL RS, data on the treatment for RS was available in 99 patients. Twenty-one patients did not received treatment due to frailty, comorbidities, or poor performance status. Of the 78 patients that were treated for RS, 46 patients received chemoimmunotherapy, mainly R-CHOP (n=44), 29 patients chemotherapy (most commonly CHOP and purine analogue-based therapy), and others (n=3). The overall response rate for the 99 treated patients was 44% (chemotherapy, 24%; chemoimmunotherapy, 60%; P=0.003). A total of 13 patients underwent stem-cell transplantation (SCT), allogeneic SCT (n=7) or autologous SCT (n=6).After a median follow-up for surviving patients of 36 months (range 0.8-160 months), median overall survival (OS) from the time of transformation of CLL to high grade lymphoma was 7.3 months for the entire cohort, 5.7 months for DLBCL RS patients, and 30.8 months for patients with HL variant (P=0.07). Factors associated with shorter OS in the DLBCL RS series included, ECOG PS >1, Hb level < 10 g/dL, platelet count < 100x109/L, LDH > 1.5 UNL, β2-microglobulin > 3mg/dL, prior CLL therapies >1, p53 positive determined by IHQ, and 17p deletion or mutation of TP53 determined in the CLL clone. RS score was also predictive for OS (median OS of 59.5 months [0-1 points], 5.4 months [2 points], 2 months [3 points], and 3 months [4-5 points], p= 0.006); on the contrary, IPI was not discriminative for OS in this series. In addition, RS clonally related presented a median OS of 5.9 months in comparison with 74.8 months for the clonally unrelated RS (p= 0.071). Finally, patients treated with chemoimmunotherapy combinations presented a median OS of 35.4 months, and the 13 patients that could consolidated the response obtained with SCT (autologous or allogeneic SCT) obtained a median OS of 59.5 months.Although clinical outcome of patients with RS is generally poor, chemoimmunotherapy combinations are effective and obtain durable responses in a proportion of patients. RS score and TP53 disruption are predictive of survival. Finally, pts attaining a response should be considered for SCT. Further clinical development with novel promising treatment options is warranted. [Display omitted] DisclosuresDelgado:Abbvie, Jansen, Gilead, Roche: Consultancy, Speakers Bureau.

MAPK and JAK-STAT pathways dysregulation in plasmablastic lymphoma.

Plasmablastic lymphoma (PBL) is an aggressive B-cell lymphoma with an immunoblastic/large-cell morphology and terminal B-cell differentiation. The differential diagnosis from Burkitt lymphoma, plasma cell myeloma and some variants of diffuse large B-cell lymphoma may be challenging because of the overlapping morphological, genetic and immunophenotypic features. Furthermore, the genomic landscape in PBL is not well known. To characterize the genetic and molecular heterogeneity of these tumors, we investigated 34 cases of PBL using an integrated approach, including fluorescence in situ hybridization, targeted sequencing of 94 B-cell lymphoma-related genes, and copy-number arrays. PBL were characterized by high genetic complexity including MYC translocations (87%), gains of 1q21.1-q44, trisomy 7, 8q23.2- q24.21, 11p13-p11.2, 11q14.2-q25, 12p and 19p13.3-p13.13, losses of 1p33, 1p31.1-p22.3, 13q and 17p13.3-p11.2, and recurrent mutations of STAT3 (37%), NRAS and TP53 (33%), MYC and EP300 (19%) and CARD11, SOCS1 and TET2 (11%). Pathway enrichment analysis suggested a cooperative action between MYC alterations and MAPK (49%) and JAK-STAT (40%) signaling pathways. Of note, Epstein-Barr virus (EBV)-negative PBL cases had higher mutational and copy-number load and more frequent TP53, CARD11 and MYC mutations, whereas EBVpositive PBL tended to have more mutations affecting the JAK-STAT pathway. In conclusion, these findings further unravel the distinctive molecular heterogeneity of PBL identifying novel molecular targets and the different genetic profile of these tumors in relation to EBV infection.

Oral Plasmablastic Lymphoma: A Case Report of an HIV Negative Patient with an Unusual Clinical Signature

Plasmablastic Lymphoma (PBL) is an aggressive variant of diffuse large B-cell lymphoma with a low survival rate. It is associated with Human Immunodeficiency Virus (HIV) infection but also affects patients with autoimmune diseases as chronic lymphocytic leukaemia, systemic lupus erythematosus and with long-term immunosuppression for heart and kidney transplants, ulcerative colitis. It has been reported in immunocompetent and HIV negative patients, determining the diagnosis more challenging. A rare case of bleeding gingival hyperplastic PBL in the left posterior mandibular area in a 61-year-old HIV negative male patient is reported. Histological assessment showed that oral mucosa was infiltrated by a monomorphic population of large lymphoid elements with morphological characteristics similar to immunoblasts with a “starry sky” appearance. Immunohistochemical markers were positive for CD138, Kappa and Lambda light chains, and negative for CKAE1/3, Synaptophysine, Chromogranin, CD56, and CD20. The detection of the primary oral manifestation of PBL remains challenging in immunocompetent patients and this case report aims to broaden the knowledge of the possible oral clinical aspects of PBL.

Plasmablastic Myeloma Versus Plasmablastic Lymphoma; Is MYC Rearrangement Helpful Towards A Precise Diagnosis?

Abstract Introduction/Objective Plasmablastic myeloma (PBM) is a rare and aggressive plasma cell neoplasm. Differentiating PBM from plasmablastic lymphoma (PBL) represents a diagnostic challenge, as both diseases have overlapping cytomorphologic and immunophenotypic features. Genetic mutations in MYC occur in a majority of PBL cases but rarely in PBM, thus can theoretically be used to differentiate between both neoplasms. Methods We report a case of a 53-year-old female who presented with a rapidly growing mass in her right mandible. Biopsy revealed circumscribed nodules of immunoblastic cells with moderate cytoplasm, large vesicular nuclei and large prominent nucleoli. Apoptotic debris and brisk mitoses were present. Molecular testing revealed a C-MYC rearrangement. The location of the neoplasm and the above described morphological features were suggestive of PBL, especially with a positive C-MYC rearrangement. The neoplastic cells were positive for CD138, MUM1,CD56 and kappa; and negative for CD45, CD20, PAX5, CD3, CD5, CD30, EBER-ISH, HHV8, ALK-1, Lambda, EMA, CD21, CD23, pancytokeratin, CK20, CK7, Cam5.2, chromogranin, synaptophysin, HMB45, S100, P16, P40. MIB-1 showed high positivity, approximately 95%. Results Patient underwent further diagnostic work up, her HIV antibodies result were negative however, she was found to be anemic (Hemoglobin 6.6 g/dl; reference range 12-16 g/dl) and hypercalcemic (Calcium 12.3 mg/dl; reference range 8.5-10.5 mg/dl). PET scan revealed multiple hypermetabolic lytic bone lesions. The bone marrow biopsy showed 80% cellularity with extensive involvement by atypical plasmacytic cells forming large clusters. The patient’s final diagnosis was PBM. Conclusion Differentiating PBM from PBL is essential as treatment is different. Although MYC rearrangement in PBM is not common, it has been demonstrated and therefore should not be used to exclude this diagnosis. Here, we highlight the importance of correlating detailed clinical, radiological, laboratory, histological and genetics data for reaching the final diagnosis.

Unilateral Maxillary Sinus Plasmablastic Lymphoma in an Immunocompetent Patient. An Unusual Occurrence Report and Literature Review.

Plasmablastic lymphoma (PBL) is a rare and aggressive form of mature B cell neoplasms almost exclusively identified in patients infected with the human immunodeficiency virus (HIV). The small number of HIV-negative PBL cases reported in the literature to date is composed of single case reports and small case series which characteristically are present involving the oral cavity mucosa or gingiva. We present a 72-year-old HIV-negative Australian patient without any cause of immunodeficiency, with an isolated left maxillary sinus PBL.

Plasmablastic lymphoma in Johannesburg, South Africa, in the era of widescale antiretroviral therapy use.

Plasmablastic lymphoma (PBL) is a clinically aggressive lymphoma which has a predilection for extranodal sites and is frequently HIV-associated. The incidence of non-Hodgkin lymphoma is thought to be reduced by widescale antiretroviral therapy (ART) coverage, but the literature is sparse as regards the impact of ART on the incidence of PBL and its outcomes in South Africa (SA). This study aimed to compare factors of interest in cases of PBL diagnosed before and after the widespread availability of ART in Johannesburg, SA. All cases of PBL diagnosed in the state sector hospitals of Johannesburg in 2007 and 2017 (before and after the widespread availability of ART, respectively) were extracted from the laboratory information system, and factors of interest compared. The majority (>95%) of cases of PBL were seen among people with HIV infection (PWH) at both time-points, and the proportion of patients on ART and with virological suppression (VS) increased significantly in 2017. However, the number of cases of PBL did not differ significantly between the twoyears assessed, comprising 46/397 (11.6%) and 53/582 (9.6%) of all lymphomas in 2007 and 2017, respectively (P=0.23). Ongoing risk for PBL among PWH with virological control and immunological recovery was evident in 2017, as 18.9% of the patients had both VS and CD4 counts >200 cells/μL at diagnosis. Inferior survival times were associated with elevated lactate dehydrogenase (LDH) levels and Epstein Barr virus (EBV) negativity, but were not influenced by the presence of AIDS, ART or VS. EBV negativity was significantly associated with VS, and appeared to flag a particularly aggressive form of the disease. Widescale ART coverage has not reduced the incidence of PBL in Johannesburg, and an ongoing risk for this disease among PWH with adequate virological control and immunological recovery persists.

ABCL-407: Daratumumab, Lenalidomide, and Dexamethasone (DRD), an Active Regimen in the Treatment of Sirolimus-Associated Plasmablastic Lymphoma (PBL) in the Setting of Gorham's Lymphangiomatosis: A Case Report

Introduction/Background: Plasmablastic lymphoma (PBL) is a rare variant of diffuse large cell B-cell lymphoma characterized by an aggressive course with a poor overall survival. Gorham-Stout Disease (GSD) is a rare skeletal condition of unknown etiology characterized by progressive bone loss and non-malignant proliferation of vascular and lymphatic channels within the affected bone. There is currently no standard of care treatment for either disease. We present a case of PBL induced by sirolimus in a patient with GSD who achieved complete response to treatment with daratumumab, lenalidomide, and dexamethasone (DRD). Case Presentation: A 23-year-old Hispanic female with past medical history of GSD manifesting as lymphedema of left upper extremity, resorption of the left clavicle, and scapular head and humerus, as well as history of chylothoraces, was treated with sirolimus and octreotide. She was admitted for hypoxic respiratory failure requiring intubation. A CT scan showed diffuse lymphadenopathy and a large mediastinal mass. Biopsy showed plasmablastic lymphoma. HIV, EBV, and HHV8 were negative. Sirolimus was discontinued. Dose-adjusted V-EPOCH was initiated but complicated by neutropenic fever and small bowel obstruction. Follow-up CT showed progression of the disease, and the patient was started on DRD. A repeat PET-CT scan after two cycles showed improvement or resolution of previously hypermetabolic lesions and lymph nodes, consistent with complete response (Deauville 2). She underwent evaluation for stem cell transplant but was not a candidate. She continued dose-adjusted DRD but relapsed at 8 months and expired with a total overall survival of 12 months. Discussion: PBL is a difficult condition to treat with a poor overall survival of approximately 15 months and no official recommended treatment regimens at this time. V-EPOCH is often utilized. Our patient had multiple complications while undergoing V-EPOCH. Given the strong CD38+ expression and reported efficacy of lenalidomide in PBL, as well as its antiangiogenic effect for GSD, DRD was selected for treatment in our patient. To our knowledge, this is the first case of PBL treated with DRD achieving complete response. Conclusion: DRD is an active regimen in PBL. Clinical investigations of a DRD regimen in PBL in conjunction with other agents to improve both depth and durability of response is warranted. Plasmablastic lymphoma (PBL) is a rare variant of diffuse large cell B-cell lymphoma characterized by an aggressive course with a poor overall survival. Gorham-Stout Disease (GSD) is a rare skeletal condition of unknown etiology characterized by progressive bone loss and non-malignant proliferation of vascular and lymphatic channels within the affected bone. There is currently no standard of care treatment for either disease. We present a case of PBL induced by sirolimus in a patient with GSD who achieved complete response to treatment with daratumumab, lenalidomide, and dexamethasone (DRD). A 23-year-old Hispanic female with past medical history of GSD manifesting as lymphedema of left upper extremity, resorption of the left clavicle, and scapular head and humerus, as well as history of chylothoraces, was treated with sirolimus and octreotide. She was admitted for hypoxic respiratory failure requiring intubation. A CT scan showed diffuse lymphadenopathy and a large mediastinal mass. Biopsy showed plasmablastic lymphoma. HIV, EBV, and HHV8 were negative. Sirolimus was discontinued. Dose-adjusted V-EPOCH was initiated but complicated by neutropenic fever and small bowel obstruction. Follow-up CT showed progression of the disease, and the patient was started on DRD. A repeat PET-CT scan after two cycles showed improvement or resolution of previously hypermetabolic lesions and lymph nodes, consistent with complete response (Deauville 2). She underwent evaluation for stem cell transplant but was not a candidate. She continued dose-adjusted DRD but relapsed at 8 months and expired with a total overall survival of 12 months. PBL is a difficult condition to treat with a poor overall survival of approximately 15 months and no official recommended treatment regimens at this time. V-EPOCH is often utilized. Our patient had multiple complications while undergoing V-EPOCH. Given the strong CD38+ expression and reported efficacy of lenalidomide in PBL, as well as its antiangiogenic effect for GSD, DRD was selected for treatment in our patient. To our knowledge, this is the first case of PBL treated with DRD achieving complete response. DRD is an active regimen in PBL. Clinical investigations of a DRD regimen in PBL in conjunction with other agents to improve both depth and durability of response is warranted.

Gastrointestinal Tract Plasmablastic Lymphoma in HIV-Infected Adults: A Histopathological Review.

Plasmablastic lymphoma (PBL) is an aggressive B-cell lymphoma that is characterized by the expression of plasma cell antigens and loss of pan B-cell antigens. The neoplasm is extensively reported in the oral cavity and anorectal region but rarely in the gastrointestinal tract, where only isolated case reports and small case series have been reported. In the current study, morphologic, immunohistochemical, and molecular features of 17 cases of gastrointestinal tract PBL were reviewed. Ten-year retrospective study that reappraised the histomorphological and immunophenotypical profiles of HIV-associated PBLs in the gastrointestinal tract. The mean age of the study patients was 41 years with a 3:1 ratio of males to females. The most common site of tumor origin was the small intestine (42%), followed by the stomach (29%) and the colon (29%). Majority of the cases showed a predominant diffuse (82%) growth pattern. Immunoblasts and plasmablasts were observed in all cases. Plasmacytic differentiation was seen in 5 (29%) cases. Additional observations not previously described or emphasized in literature includes pseudo-alveolar growth pattern, centroblast-predominance, multinucleated giant cells, and clear cell change. Immunohistochemistry revealed absence of pan B-cell antigens and expression of plasma cell antigens in all cases. Epstein-Barr virus-encoded RNA was expressed in 53% of the cases. This study highlights the spectrum of histopathological features seen in gastrointestinal tract PBLs. Awareness of this entity and its histopathological features in the gastrointestinal tract is essential for making a timely and accurate diagnosis and improving patient outcomes.

Plasmablastic Lymphoma: A Clinicopathological Study from a Tertiary Care Cancer Center in South India.

Background Plasmablastic lymphoma (PBL) is a rare aggressive B cell lymphoma that is commonly encountered in patients with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS). In this case series, we describe the clinicopathological features of cases of PBL seen at a tertiary care center in South India. Materials and Methods Medical records of patients diagnosed with PBL between January 2009 and November 2017 were reviewed. PBL was defined as per the World Health Organization 2016 classification for hematopoietic and lymphoid neoplasms. The slides were reviewed with hematoxylin and eosin along with immunohistochemistry (IHC) including CD45, CD20, PAX5, CD79a, CD3, CD5, CD138, MUMI, EMA, ALK, and Ki67. Epstein-Barr virus (EBV) association was documented by rapid in situ hybridization (RISH) studies wherever possible. The demographic data, clinical presentation, treatment details, and outcomes are elaborated using descriptive statistics. Results During the study period, nine patients with PBL were identified. The median age at presentation was 47 years (range: 36–54 years). All patients had associated HIV/AIDS, eight (89%) had extranodal disease, and six (66%) had advanced clinical stage (stage III). All biopsies were positive for CD45, CD138, and MUM1, and negative for CD79a and T cell markers with a high Ki67 proliferation index (85–90%); CD20 was faint positive in one patient, and CD56 was positive in one (11%) patient. EBV-RISH was tested in two patients and was positive in one. Bone marrow was uninvolved in all the cases. At the time of last follow-up, three patients were alive. Treatment details were available in six patients. With frontline therapy, four patients achieved a complete remission (CR) and one patient developed progressive disease. Three of four patients in CR are alive till the last follow-up. Conclusion PBL is a rare form of lymphoma with predominant association with HIV, extranodal location, and characteristic IHC pattern.