Non Hodgkin's Lymphoma

Iwahara Y, Shinohara T, Naruse K, Komatsu Y
Non-Hodgkin's lymphoma involving a femur bone and bilateral adrenal glands alone with adrenal insufficiency.
BMJ Case Rep. 2017; 2017 [PubMed] Related Publications

Primary bone lymphoma and primary adrenal lymphoma are rare clinicopathological entities of non-Hodgkin's lymphoma (NHL). We present the first case of diffuse large B-cell lymphoma with the involvement of a single bone and both adrenal glands alone with adrenal insufficiency. As primary extranodal NHL may have other unusual extranodal lesions, which may present unexplained clinical findings, patients with primary extranodal NHL require careful systemic examination, even when lymphadenopathy is absent.

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Nakatsuka SI, Yutani C, Kurashige M, et al.
An unusual case of Epstein-Barr virus-positive large B-cell lymphoma lacking various B-cell markers.
Diagn Pathol. 2017; 12(1):15 [PubMed] Free Access to Full Article Related Publications

BACKGROUD: Epstein-Barr virus (EBV) is associated with B-cell lymphoma in various conditions, such as immunodeficiency and chronic inflammation. We report an unusual case of EBV-positive diffuse large B-cell lymphoma (DLBCL) lacking the expression of many B-cell markers.
CASE PRESENTATION: An 83-year-old man presented with a submandibular tumor. Histology of a lymph node biopsy specimen revealed diffuse proliferation of centroblast- or immunoblast-like lymphoid cells with plasmacytic differentiation. Scattered Hodgkin/Reed-Sternberg-like cells were also visible. A routine immunohistochemistry antibody panel revealed that the tumor cells were negative for B-cell and T-cell markers (i.e., CD3, CD19, CD20, CD38, CD45RO, CD79a, CD138, and Pax-5), but were positive for CD30 and MUM-1, not defining the lineage of tumor cells. The final diagnosis of EBV-positive DLBCL was confirmed based on the expression of B-cell-specific transcription factors (Oct-2 and BOB.1), PCR-based identification of monoclonal rearrangement of the immunoglobulin genes, and the presence of EBV-encoded small RNAs in the tumor cells (identified using in situ hybridization).
CONCLUSION: The downregulation of broad band of B-cell markers in the present case with EBV-positive DLBCL posed a diagnostic dilemma, as the possible diagnoses included differentiation from anaplastic large cell lymphoma and CD20-negative B-cell lymphomas. Results of immunohistochemical panel including B-cell-specific transcription factors and gene rearrangement analyses critically support the correct diagnosis.

Rieger KE, Kim J, Kim YH
Zosteriform Mycosis Fungoides: A New Clinical Presentation With a Dermatomal Distribution.
Am J Dermatopathol. 2017; 39(2):e17-e18 [PubMed] Related Publications

Classic mycosis fungoides (MF) presents with patches and plaques on the trunk and proximal extremities. However, numerous clinicopathologic variants have been described, making diagnosis challenging. Here, the authors report a 21-year-old woman with immunophenotypically and molecularly confirmed MF occurring in a dermatomal distribution. Awareness of this and other rare variants of MF is critical to avoid misdiagnosis.

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Cutaneous T-cell lymphoma

Shamsuyarova A, Kamil Z, Delabie J, et al.
Primary Cutaneous Follicular Helper T-cell Lymphoma in a Patient With Neurofibromatosis Type 1: Case Report and Review of the Literature.
Am J Dermatopathol. 2017; 39(2):134-139 [PubMed] Related Publications

Patients with neurofibromatosis type 1 (NF-1) have a well-known predisposition for certain types of malignancies, including lymphoproliferative disorders. Cutaneous T-cell lymphoma (CTCL) has been reported in patients with NF-1, although it is considered a rare entity in this subset of patients. Cutaneous follicular helper T-cell lymphoma (CTFHCL) is a recently emerged rare subtype of CTCL with peculiar clinical and histopathological features and represents a diagnostic and therapeutic challenge. Only a few cases of CTFHCL have been reported in the literature. We report a case of CTFHCL in a patient with NF-1 and compare our findings with previously reported cases. We aim to raise awareness among pathologists regarding this rare subtype of CTCL and emphasize characteristic histological features of CTFHCL, which can be confused with B-cell lymphomas and lead to mismanagement.

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Ding X, Makino T, Koezuka S, et al.
Primary extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue with multiple pure ground-glass opacities: a case report.
J Cardiothorac Surg. 2017; 12(1):2 [PubMed] Free Access to Full Article Related Publications

BACKGROUND: Primary pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma is a low-grade B cell lymphoma that is a type of non-Hodgkin lymphoma and a type of primary pulmonary malignant lymphoma. MALT lymphomas affecting the lung show various findings on chest computed tomography, which range from typical nodules or areas of consolidation to findings that are extremely rare in pulmonary MALT lymphomas, such as pure ground-glass opacities throughout the lung.
CASE PRESENTATION: A 35-year-old woman was found to have a few shadows with ground glass opacities on chest computed tomography (CT) in 2012. A shadow in right S10 that was initially very small increased in size over time, and was 14 × 8 mm in 2015. Other shadows also appeared. Because lung adenocarcinoma was suspected, the patient underwent video-assisted thoracoscopic surgery with a right wedge resection of the lower lobe that included the largest nodule in S10 and other nodules. Histopathological examination of the right S10 and other lesions revealed small- or medium-sized lymphocyte-like cells that were located in the alveolar interseptal spaces. The alveolar walls remained intact. Immunohistochemical staining showed that tumor cells were positive for CD20, CD79a, and BCL2 expression. The lesions were diagnosed as extranodal marginal zone B-cell lymphoma of MALT.
CONCLUSIONS: We think that the ground glass opacities on CT were accounted for by MALT lesions that contained intact alveolar air spaces. The patient has remained well during 12 months of follow up after surgery. Although she did not receive chemotherapy because the MALT lymphoma lesions have been stable without progression, the patient is kept under close observation because of potential progression of the disease.

Related:

Lung Cancer

MALT Lymphoma

Bhagat VH, Sepe T
Pancreatic lymphoma complicating early stage chronic hepatitis C.
BMJ Case Rep. 2017; 2017 [PubMed] Related Publications

Hepatitis C virus (HCV) infection has also been associated with many extrahepatic manifestations including the development of B-cell non-Hodgkin's lymphoma (NHL). Primary pancreatic lymphoma is very rare and comprises 2.2% of NHL and 4.9% of all pancreatic malignancies. Our patient was a woman with a history of infection with HCV found to have a mass in the head of the pancreas. Biopsy of the mass revealed a high-grade B-cell lymphoma consistent with Burkitt's lymphoma. Our case reflects a need to initiate antiviral therapy for all patients infected with HCV even in early stages of fibrosis to prevent cirrhosis and other extrahepatic manifestations of infection with HCV.

Related:

Etoposide

Cancer of the Pancreas

Pancreatic Cancer

Rituximab (Mabthera)

Chronic Myeloid Leukemia (CML)

Kinsella FA, Amel Kashipaz MR, Scarisbrick J, Malladi R
Donor-derived mycosis fungoides following reduced intensity haematopoietic stem cell transplantation from a matched unrelated donor.
BMJ Case Rep. 2017; 2017 [PubMed] Free Access to Full Article Related Publications

A 46-year-old woman with a history of dasatinib-resistant chronic myeloid leukaemia, clonal evolution and monosomy 7 underwent reduced intensity conditioned in vivo T-cell-depleted allogeneic haematopoietic stem cell transplantation (HSCT) from a matched unrelated donor. Following the transplantation, she developed recurrent cutaneous graft versus host disease (GvHD), which required treatment with systemic immunosuppression and electrocorporeal photophoresis. Concurrently, she developed a lichenoid rash with granulomatous features suggestive of cutaneous sarcoidosis. Additional treatment with hydroxychloroquine was initially successful, but 2 months later, she developed erythroderma with palpable lymphadenopathy. Repeated histological analysis established a diagnosis of folliculotropic mycosis fungoides stage IVA2, and the malignant clone was confirmed to be of donor origin. A positive response to brentuximab has been shown. This is the first reported case of primary mycosis fungoides after matched unrelated donor HSCT, and in a patient still undergoing treatment for GvHD.

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CML - Molecular Biology

Zamani-Ahmadmahmudi M, Aghasharif S, Ilbeigi K
Prognostic efficacy of the human B-cell lymphoma prognostic genes in predicting disease-free survival (DFS) in the canine counterpart.
BMC Vet Res. 2017; 13(1):17 [PubMed] Free Access to Full Article Related Publications

BACKGROUND: Canine B-cell lymphoma is deemed an ideal model of human non-Hodgkin's lymphoma where the lymphomas of both species share similar clinical features and biological behaviors. However there are some differences between tumor features in both species. In the current study, we sought to evaluate the prognostic efficacy of human B-cell lymphoma prognostic gene signatures in canine B-cell lymphoma.
METHODS: The corresponding probe sets of 36 human B-cell lymphoma prognostic genes were retrieved from 2 canine B-cell lymphoma microarray datasets (GSE43664 and GSE39365) (76 samples), and prognostic probe sets were thereafter detected using the univariate and multivariate Cox proportional-hazard model and the Kaplan-Meier analysis. The two datasets were employed both as training sets and as external validation sets for each other. Results were confirmed using quantitative real-time PCR (qRT-PCR) analysis.
RESULTS: In the univariate analysis, CCND1, CCND2, PAX5, CR2, LMO2, HLA-DQA1, P53, CD38, MYC-N, MYBL1, and BIRCS5 were associated with longer disease-free survival (DFS), while CD44, PLAU, and FN1 were allied to shorter DFS. However, the multivariate Cox proportional-hazard analysis confirmed CCND1 and BIRCS5 as prognostic genes for canine B-cell lymphoma. qRT-PCR used for verification of results indicated that expression level of CCND1 was significantly higher in B-cell lymphoma patients with the long DFS than ones with the short DFS, while expression level of BIRCS5 wasn't significantly different between two groups.
CONCLUSION: Our results confirmed CCND1 as important gene that can be used as a potential predictor in this tumor type.

Al-Rawi NH
Primary non-Hodgkin's lymphoma of the tongue: a diagnostic dilemma of unusual case presentation.
BMJ Case Rep. 2017; 2017 [PubMed] Related Publications

Primary non-Hodgkin's lymphoma of the tongue is extremely uncommon, which makes its diagnosis quite challenging. A panel of 11 markers is used based on morphological differential diagnosis to elucidate the lymphoma subtype. A case of 43-year-old Egyptian man suffering from nodular mass on the right side of the tongue of 4 months duration is presented. No cervical lymphadenopathy was detected. No abdominal organomegaly was noted. The histological evaluation of incisional biopsy revealed a sheet of pleomorphic lymphoid cells with abnormal mitotic figures. A large number of histiocytes were infiltrating the lymphoid cellular sheet. The results of immunophenotyping were extranodal T-cell lymphoma. A proper immunohistochemical workup is crucial for the correct diagnosis and proper management.

Related:

Chronic Lymphocytic Leukemia (CLL)

Majeed A, Abdullah HM, Ullah W, Al Mohajer M
First reported case of disseminated Nocardia kroppenstedtii sp nov. infection presenting with brain abscess and endocarditis in an immunocompromised patient with mantle cell lymphoma: challenges in diagnosis and treatment.
BMJ Case Rep. 2017; 2017 [PubMed] Related Publications

A 72-year-old man with a history of blastoid variant stage IV relapsed refractory mantle cell lymphoma presented with new central nervous system (CNS) symptoms. Brain imaging was positive for rim-enhancing lesions along with a mitral valve mass on the echocardiogram. It was a challenge to establish the exact aetiology of these lesions in this patient. He was empirically treated with chemotherapy on the presumption that the brain lesions were secondary to progressive malignancy. However, brain biopsy was negative for malignancy and blood cultures were found positive for Nocardia kroppenstedtii sp nov. He subsequently improved with antibiotic therapy. Disseminated Nocardia can present with multiorgan involvement. Clinical and microbiological diagnosis can be challenging. Antimicrobial treatment-related side effects require close monitoring, and dosage changes or therapy adjustments may be necessary.

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Mantle Cell Lymphoma

Oliveira CC, Maciel-Guerra H, Kucko L, et al.
Double-hit lymphomas: clinical, morphological, immunohistochemical and cytogenetic study in a series of Brazilian patients with high-grade non-Hodgkin lymphoma.
Diagn Pathol. 2017; 12(1):3 [PubMed] Free Access to Full Article Related Publications

BACKGROUND: Double-hit lymphomas (DHL) are rare high-grade neoplasms characterized by two translocations: one involving the gene MYC and another involving genes BCL2 or BCL6, whose diagnosis depends on cytogenetic examination. This research studied DHL and morphological and/or immunophenotypic factors associated with the detection of these translocations in a group of high-grade non-Hodgkin lymphoma cases.
METHOD: Clinical and morphological reviews of 120 cases diagnosed with diffuse large B-cell lymphoma and Burkitt lymphoma were conducted. Immunohistochemistry (CD20, CD79a, PAX5, CD10, Bcl6, Bcl2, MUM1, TDT and Myc) and fluorescence in situ hybridization for detection of MYC, BCL2 and BCL6 gene translocations were performed in a tissue microarray platform.
RESULTS: Three cases of DHL were detected: two with translocations of MYC and BCL2 and one with translocations of MYC and BCL6, all leading to death in less than six months. Among 90 cytogenetically evaluable biopsies, associations were determined between immunohistochemistry and fluorescence in situ hybridization for MYC (p = 0.036) and BCL2 (p = 0.001). However, these showed only regular agreement, indicated by Kappa values of 0.23 [0.0;0.49] and 0.35 [0.13;0.56], respectively. "Starry sky" morphology was strongly associated with MYC positivity (p = 0.01). The detection of three cases of DHL, all resulting in death, confirms the rarity and aggressiveness of this neoplasm.
CONCLUSIONS: The "starry sky" morphological pattern and immunohistochemical expression of Myc and Bcl2 represent possible selection factors for additional cytogenetic diagnostic testing.

Related:

BCL6

MYC

Saviola G, Prometti P, Ferrari PR, Dalle Carbonare LG
Atypical femoral fracture as first sign of non-hodgkin lymphoma- case report with a brief review of the literature.
Clin Ter. 2016 Nov-Dec; 167(6):188-190 [PubMed] Related Publications

ABSTRACT: Atypical subtrochanteric and diaphyseal femoral fractures (AFF) have been suggested to be associated with the use of bisphosphonates (BPs), but the role of these drugs is still under debate. A 64-year old female, never treated with BPs was admitted to our Rehabilitation Institute because of a recent right AFF. The patient began suffering from low back pain radiating to the groin and to the anterior regions of the right thigh and leg, A nuclear magnetic resonance (NMR) of the lumbar spine showed disc protrusions at the L3-L4 and L5-S1 levels with impingement of the spinal nerve root. Therefore she was treated with analgesic, anti-inflammatory and muscle relaxing compounds for nine months without reduction of symptoms. Being the pain still present, the patient felt down the street breaking the right femoral neck and the femoral distal shaft. Following the ASBMR criteria the fracture was classified as a complete AFF and the patient underwent surgical ostheosynthesis with nail. A bone biopsy of the fracture site was performed showing findings consistent with B-cells non-Hodgkin lymphoma (NHL). Immuno-histochemical analysis highlighted that the atypical cells were follicolar G2 pattern diffuse large B cells.
CONCLUSIONS: AFF can occur also in patients not treated with BPs. In the present case report, the cause of the fracture was a NHL. Even uncommon, this occurrence should be considered in the differential diagnosis of radicular pain.

Harada Y, Sakai K, Asaka S, Nakayama K
Angioimmunoblastic T-cell Lymphoma Associated with IgA Nephropathy.
Intern Med. 2017; 56(1):85-89 [PubMed] Free Access to Full Article Related Publications

Few cases of IgA nephropathy with angioimmunoblastic T-cell lymphoma (AITL) have been reported. We herein present the case of a 79-year-old Japanese man with AITL and IgA nephropathy. The patient presented with generalized edema, fatigue, and fever. Laboratory investigations revealed polyclonal gammopathy with a high level of IgA, microscopic hematuria, proteinuria, and some other immunological abnormalities. Computed tomography revealed generalized lymphadenopathy. A diagnosis of AITL and IgA nephropathy was made based on inguinal lymph node and renal biopsies. Following chemotherapy for AITL, the patient's edema, microscopic hematuria, and proteinuria were alleviated. These findings indicate that IgA nephropathy may occur in AITL patients.

O'Malley DP, Lee JP, Bellizzi AM
Expression of LEF1 in mantle cell lymphoma.
Ann Diagn Pathol. 2017; 26:57-59 [PubMed] Related Publications

Small lymphocytic lymphoma/chronic lymphocytic leukemia (CLL/SLL) and mantle cell lymphoma (MCL) usually are distinctly different in regard to clinical presentation, morphology, immunophenotype and molecular/genetic findings. In spite of this, select cases may show overlapping characteristics and represent a diagnostic challenge. Recently LEF1 staining was identified as a fairly characteristic finding in CLL/SLL, with positivity identified in up to 95% of cases. LEF1 staining has not been reported as being present in cases of MCL, making this stain a useful tool in distinguishing these diagnoses. We identified an index case of MCL with cyclin D1 expression and the presence of the typical t(11;14) IGH-CCND1, which expressed LEF1. Subsequently, we assessed LEF1 immunohistochemical staining in a series of 23 cases of MCL, as confirmed by staining for cyclin D1 and/or SOX11. We found expression present in one additional case, and evaluated some published literature suggesting a frequency of 4-9% expression of LEF1 by MCL. LEF1 expression by immunohistochemistry in MCL is unusual but can be seen rarely, and could represent a potential diagnostic pitfall.

Related:

CLL - Molecular Biology

Mantle Cell Lymphoma

LEF1

Yabe M, Medeiros LJ, Daneshbod Y, et al.
Hepatosplenic T-cell lymphoma arising in patients with immunodysregulatory disorders: a study of 7 patients who did not receive tumor necrosis factor-α inhibitor therapy and literature review.
Ann Diagn Pathol. 2017; 26:16-22 [PubMed] Related Publications

Hepatosplenic T-cell lymphoma (HSTCL) is a rare and aggressive extranodal T-cell lymphoma that can arise in patients with underlying immune disorders. Others have suggested that tumor necrosis factor (TNF)-α inhibitor therapy for immune disorders increases the risk of HSTCL. To assess for a potential relationship between HSTCL and the use of TNF-α inhibitors, we searched for patients with HSTCL and underlying immune disorders at our institution. We identified 7 patients with a median age of 38 years. Five patients had Crohn disease, 1 ulcerative colitis, and 1 rheumatoid arthritis. In 6 patients, medication history for the immune disorder was available: 6 patients received 6-mercaptopurine or azathioprine, and 2 patients received steroids; no patients received TNF-α inhibitors. In all 7 patients, the histologic, immunophenotypic, and cytogenetic findings were similar to cases of HSTCL that arise in immunocompetent patients. We reviewed the literature and identified 60 patients with immune disorders who subsequently developed HSTCL. These patients were treated with immunosuppressive drugs in 89%, TNF-α inhibitors in 56%, and both therapies in 54%, and 1 (2%) patient was treated with TNF-α inhibitors only. Our cohort and literature review indicates that TNF-α inhibitor therapy is not essential for the development of HSTCL in patients with immunodysregulatory disorders, and implies that immunosuppressive drugs or other factors (eg, genetic predisposition, chronic antigenic stimulation) may be more critical in the pathogenesis in this context. Although these data are observational, they have implications for the use of TNF-α inhibitors in patients with inflammatory bowel disease and other immunodysregulatory disorders.

Related:

Monoclonal Antibodies

Liver Cancer

TNF

Dlouhy I, Torrente MÁ, Lens S, et al.
Clinico-biological characteristics and outcome of hepatitis C virus-positive patients with diffuse large B-cell lymphoma treated with immunochemotherapy.
Ann Hematol. 2017; 96(3):405-410 [PubMed] Related Publications

Diffuse large B cell lymphoma (DLBCL) patients carrying hepatitis C virus (HCV) have higher risk of treatment toxicity and complications. The aim of this study was to assess the impact of HCV in a series of DLBCL patients treated with immunochemotherapy. 321 patients (161 M/160F; median age, 66 years) diagnosed with de novo DLBCL in a single center between 2002 and 2013 were included. Immunodeficiency-related lymphomas were excluded. HCV+ cases were defined by the presence of IgG anti-HCV. Main clinico-biological characteristics and outcome were analyzed according to the viral status. Two hundred ninety patients were HCV- and 31 HCV+. HCV+ patients were older (median age 71 vs. 64 years, P = 0.03), had more often B symptoms (P = 0.013), spleen (P = 0.003), and liver (P = 0.011) involvement, higher rate of early death (<4 months, P = .001), and shorter overall survival (OS). Eleven HCV+ patients had cirrhosis criteria. HCV+ patients with impaired liver function before or during treatment showed inferior OS. Elevated pre-treatment bilirubin correlated also with higher liver toxicity. In a multivariate analysis that included R-IPI score, serum beta2-microglobulin (β2m), HCV status, and presence of cirrhosis, only R-IPI, β2m, and cirrhosis showed independent prognostic impact on OS. The presence of HCV in DLBCL patients entails higher number of complications and early deaths; however, liver impairment and not the hepatitis viral status was the key feature in the outcome of the patients.

Fernández C, Bellosillo B, Ferraro M, et al.
MicroRNAs 142-3p, miR-155 and miR-203 Are Deregulated in Gastric MALT Lymphomas Compared to Chronic Gastritis.
Cancer Genomics Proteomics. 2017; 14(1):75-82 [PubMed] Free Access to Full Article Related Publications

BACKGROUND: Over the last years, our knowledge on pathogenesis of gastric MALT lymphoma has greatly improved, but its morphological diagnosis is still hampered by overlapping histological features with advanced chronic gastritis. MicroRNAs are deregulated in lymphomas, but their role and usefulness in gastric MALT lymphoma has not been extensively investigated.
MATERIALS AND METHODS: We analyzed the expression of 384 miRNAs using TaqMan microRNA assay in a training series of 10 gastric MALT lymphomas, 3 chronic gastritis and 2 reactive lymph nodes. Then, significantly deregulated miRNAs were individually assessed by real-time PCR in a validation series of 16 gastric MALT lymphomas and 12 chronic gastritis.
RESULTS: Gastric MALT lymphoma is characterized by a specific miRNA expression profile. Among the differentially expressed miRNAs, a significant overexpression of miR-142-3p and miR-155 and down-regulation of miR-203 was observed in gastric MALT lymphoma when compared to chronic gastritis.
CONCLUSION: miR-142-3p, miR-155 and miR-203 expression levels might be helpful biomarkers for the differential diagnosis between gastric MALT lymphomas and chronic gastritis.

Related:

Miao Y, Lin P, Wang W, et al.
CCND1-IGH Fusion-Amplification and MYC Copy Number Gain in a Case of Pleomorphic Variant Mantle Cell Lymphoma.
Am J Clin Pathol. 2016; 146(6):747-752 [PubMed] Related Publications

OBJECTIVES: Mantle cell lymphoma (MCL) may present de novo or undergo progression to a clinically aggressive variant, known as a blastoid or pleomorphic variant. We report an unusual case of classic MCL in a 78-year-old man with a typical immunophenotype, including CD5 positivity, who subsequently relapsed with CD5-negative pleomorphic variant MCL.
METHODS: Biopsy specimens were evaluated using Wright-Giemsa-stained or H&E-stained sections, flow cytometry, immunohistochemistry, conventional cytogenetic, next-generation sequencing, and fluorescence in situ hybridization.
RESULTS: The patient continued to be refractory to intensive chemotherapy and radiation therapy. Initial conventional cytogenetic analysis showed a complex karyotype with amplification of the CCND1-IGH fusion gene on the der(14): 44, Y, t(X;2)(p22.3;q21), del(2)(p21), del(6)(p23), add(7)(p22),-9, del(9)(p22), add(11)(q13),-13, add(14)(p11.2), der(14)t(11;14)(q13;q32)hsr(14)(q32), add(18)(q23), add(21)(p11.1),-22,+mar[12]. A repeat biopsy revealed MCL, pleomorphic variant, with loss of CD5 expression and extra copies of the MYC CONCLUSIONS: CCND1-IGH fusion-amplification with MYC copy number gain is extremely rare and may play a role in disease progression in a subset of MCL cases.

Related:

Mantle Cell Lymphoma

Berger GK, McBride A, Lawson S, et al.
Brentuximab vedotin for treatment of non-Hodgkin lymphomas: A systematic review.
Crit Rev Oncol Hematol. 2017; 109:42-50 [PubMed] Article available free on PMC after 01/01/2018 Related Publications

BACKGROUND: Brentuximab vedotin (BV) is an antibody-drug conjucate (ADC) comprising a CD30-directed antibody, conjugated to the microtubule-disrupting agent MMAE via a protease cleavable linker. BV is FDA approved for use in relapsed classical Hodgkin lymphoma (HL) and relapsed systemic anaplastic large cell lymphoma (sALCL). There are multiple publications for its utility in other malignancies such as diffuse large B-cell lymphoma (DLBCL), mycosis fungoides (MF), Sézary syndrome (SS), T-cell lymphomas (TCL), primary mediastinal lymphoma (PMBL), and post-transplant lymphoproliferative disorders (PTLD). We believe that BV could potentially provide a strong additional treatment option for patients suffering from NHL.
OBJECTIVE: Perform a systematic review on the use of BV in non-Hodgkin lymphoma (NHL) and other CD30(+) malignancies in humans.
DATA SOURCES: We searched various databases including PubMed (1946-2015), EMBASE (1947-2015), and Cochrane Central Register of Controlled Trials (1898-2015).
ELIGIBILITY CRITERIA: Inclusion criteria specified all studies and case reports of NHLs in which BV therapy was administered.
INCLUDED STUDIES: A total of 28 articles met these criteria and are summarized in this manuscript.
CONCLUSION: Our findings indicate that BV induces a variety of responses, largely positive in nature and variable between NHL subtypes. With additional, properly powered prospective studies, BV may prove to be a strong candidate in the treatment of various CD30(+) malignancies.

Kanazawa Y, Yamashita Y, Fujiwara M, et al.
Two Relapsed Stage III Childhood Anaplastic Large Cell Lymphoma Patients with NPM-ALK Fusion in Bone Marrow from Initial Diagnosis.
Acta Med Okayama. 2016; 70(6):503-506 [PubMed] Related Publications

Childhood anaplastic large cell lymphoma (ALCL) accounts for approx. 10-30% of cases of non-Hodgkin lymphoma, and the ALCL99 study reported 60-75 disease-free survival; however, a relatively high relapse rate was observed (25-30% ). We report 2 patients with Stage III ALCL who relapsed 6-18 months after the end of ALCL99 chemotherapy. A retrospective molecular analysis identified the nucleophosmin (NPM)-anaplastic lymphoma kinase (ALK) fusion gene in the first diagnostic bone marrow samples taken from both patients. However, antibodies against the ALK protein appeared to be relatively low in the serum of both patients (×100 and ×750). An increase in chemotherapy intensity may be beneficial if Stage III ALCL patients are shown to be NPM-ALK chimera-positive in the first diagnostic bone marrow sample.

Related:

ALK

Tuck M, Lim J, Lucar J, Benator D
Anaplastic large cell lymphoma masquerading as osteomyelitis of the shoulder: an uncommon presentation.
BMJ Case Rep. 2016; 2016 [PubMed] Related Publications

The presentation of anaplastic lymphoma kinase protein (ALK)-negative anaplastic large cell lymphoma (ALCL) in bone is rare. We describe a patient with ALK-negative ALCL presenting with clinical and radiographic findings suggesting osteomyelitis 6 months after left rotator cuff repair surgery. A review of the characteristics of ALK-negative ALCL with primary bone involvement is presented. ALCL should be considered in patients not responding to therapies for osteomyelitis.

Related:

Soydal C, Koksoy EB, Yasar A, et al.
Prognostic Importance of Bone Marrow Uptake on Baseline (18)F-FDG Positron Emission Tomography in Diffuse Large B Cell Lymphoma.
Cancer Biother Radiopharm. 2016; 31(10):361-365 [PubMed] Related Publications

AIM: To define the role of (18)F-flourodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) in the detection of bone marrow (BM) involvement in patients with diffuse large B cell lymphoma (DLBCL).
MATERIALS AND METHODS: Fifty-four (mean age: 55.5 ± 18.3 years, 20 female and 34 male) DLBCL patients who underwent pretreatment (18)F-FDG PET/CT were included to the study. Focal or diffuse BM (18)F-FDG uptake that is higher than mediastinal blood pool uptake was accepted as positive. After staging of disease by CT and (18)F-FDG PET/CT, all the patients received R-CHOP treatment after diagnostic blinded bone marrow biopsy (BMB). Presence of positive BM uptake in (18)F-FDG PET/CT and histopathological examination results of BMBs were analyzed by Chi-square test. Sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) of (18)F-FDG PET/CT in the detection of BM involvement were calculated. Prognostic importance of the presence of BM (18)F-FDG uptake was analyzed by Kaplan-Meier analysis.
RESULTS: BM (18)F-FDG uptake was detected in 8 patients. Histopathological examination of BMB revealed BM involvement in 6 out of 8 patients. BMB was negative in all patients who have no (18)F-FDG uptake in the evaluation of PET/CT images. Sensitivity, specificity, accuracy, PPV, and NPV of (18)F-FDG PET/CT in the detection of BM involvement were calculated as 100%, 96%, 96%, 75%, and 100%, respectively. In the Kaplan-Meier analysis, we found that presence of pretreatment (18)F-FDG uptake in BM has a prognostic importance. Whereas mean time to progression (TTP) in patients with BM uptake was 32.25 ± 10.9 months and mean TTP in those without was 51.69 ± 3.6 months (p = 0.013).
CONCLUSIONS: BM uptake in pretreatment (18)F-FDG PET/CT is an important prognostic factor in DLBCL patients. Moreover, in consideration of high NPV, (18)F-FDG PET/CT could eliminate unnecessary BMB in FDG-negative patients.

Related:

Hatem J, Schrank-Hacker AM, Watt CD, et al.
Marginal zone lymphoma-derived interfollicular diffuse large B-cell lymphoma harboring 20q12 chromosomal deletion and missense mutation of BIRC3 gene: a case report.
Diagn Pathol. 2016; 11(1):137 [PubMed] Article available free on PMC after 01/01/2018 Related Publications

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) typically leads to effacement of the nodal architecture by an infiltrate of malignant cells. Rarely (<1%), DLBCL can present with an interfollicular pattern (DLBCL-IF) preserving the lymphoid follicles. It has been postulated that DLBCL-IF is derived from marginal zone B cells and may represent a large-cell transformation of marginal zone lymphoma (MZL), however no direct evidence has been provided to date. Here we describe a rare case of a diagnostically challenging DLBCL-IF involving a lymph node in a patient with a prior history of lymphadenopathy for several years and MZL involving skin.
CASE PRESENTATION: A 53-year old man presented to our Dermatology Clinic due to a 1-year history of generalized itching, fatigue of 2-3 month's duration, nausea and mid back rash that was biopsied. PET (positron emission tomography)/CT (computed tomography) was performed and revealed inguinal, pelvic, retroperitoneal, axillary, and cervical lymphadenopathy. The patient was referred to surgery for excisional biopsy of a right inguinal lymph node. Diagnostic H&E stained slides and ancillary studies were reviewed for the lymph node and skin specimens. B-cell clonality by PCR and sequencing studies were performed on both specimens. We demonstrate that this patient's MZL and DLBCL-IF are clonally related, strongly suggesting that transformation of MZL to DLBCL had occurred. Furthermore, we identified a novel deletion of the long arm of chromosome 20 (del(20q12)) and a missense mutation in BIRC3 (Baculoviral IAP repeat-containing protein 3) in this patient's DLBCL that are absent from his MZL, suggesting that these genetic alterations contributed to the large cell transformation.
CONCLUSIONS: To our knowledge, this is the first report providing molecular evidence for a previously suspected link between MZL and DLBCL-IF. In addition, we describe for the first time del(20q12) and a missense mutation in BIRC3 in DLBCL. Our findings also raise awareness of DLBCL-IF and discuss the diagnostic pitfalls of this rare entity.

Related:

Chromosome 20

FISH

MALT Lymphoma

BIRC3

Xu L, Zou XG, Wang X, et al.
Genetic characteristics of non-Hodgkin lymphoma in ethnic Uighur people, and their clinical significance.
Genet Mol Res. 2016; 15(4) [PubMed] Related Publications

The incidence of non-Hodgkin lymphoma (NHL) in China is increasing and is attracting attention as a topic of research. The percentage of NHL cases in ethnic Uighur people is also gradually increasing. We therefore recruited Uighur people with NHL to investigate the correlation between genetic alternations and clinical/pathological features in an attempt to determine their clinical significance. A total of 60 NHL patients were recruited from our hospital for a microscopic examination of their tumor cell morphology. Further analysis of chromosome karyotypes revealed the relationship between genetic alternations and clinical/pathological features. Microscopic examination revealed increased numbers of tumor cells with altered morphology. The recruited patients all exhibited abnormal karyotypes. Chromosomal breakages were detected at 14q32, 18q21, 6q21-25, +3, +, +18, and short tandem repeat 17 (str17) in 18.3, 25, 25, 18.3, 15, and 21.7% of patients, respectively. Karyotype change was not related to age, gender, performance status score, or pathological type (P > 0.05), but was correlated with clinical stage, average lactate dehydrogenase (LDH) level, extra-lymphatic metastasis, median survival time, and efficacy of radio- or chemotherapy (P < 0.05). Independent risk factors for genetic change in Uighur NHL patients included clinical stage, average LDH level, extra-lymphatic metastasis, median survival time, and efficacy of radio- or chemotherapy (P < 0.05). Uighur NHL patients exhibited genetic changes including t(14:18), 6q21-25, +3, +7, +18, and str17. Clinical stage, average LDH level, extra-lymphatic metastasis, median survival time, and efficacy of radio- or chemotherapy were all independent risk factors for NHL.

Alrifai T, Grant Szymanski K, Venugopal P, et al.
Bendamustine and Rituximab: Complete Response in a 62-Year-Old Female with an Aggressive Lymphoma and an Ejection Fraction of 20.
Chemotherapy. 2017; 62(2):140-146 [PubMed] Related Publications

The treatment of diffuse large B-cell lymphoma in the presence of cardiac comorbidities can be challenging considering that the standard treatment regimen used for this aggressive subtype of non-Hodgkin lymphoma (NHL) consists of a combination of rituximab, cyclophosphamide, doxorubicin hydrochloride, Oncovin (vincristine), and prednisone (R-CHOP). The use of the anthracycline doxorubicin has been associated with arrhythmias and cardiomyopathy, making patients with cardiac dysfunction poor candidates for R-CHOP. As such, it is imperative to find alternative regimens that omit cardiac toxicity without compromising efficacy for this patient population. We report a case of composite NHL in a patient who received frontline bendamustine with rituximab with encouraging results. Our patient had a left ventricular ejection fraction of 20%, making her a poor candidate for anthracycline-based therapy. We opted to administer bendamustine with rituximab for a total of 6 cycles. She remains disease free 18 months after the completion of therapy.

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Rituximab (Mabthera)

Dong X, Li J, Huo N, et al.
Primary central nervous system ALK-positive anaplastic large cell lymphoma in an adult: A rare case report.
Medicine (Baltimore). 2016; 95(49):e5534 [PubMed] Article available free on PMC after 01/01/2018 Related Publications

RATIONALE: Anaplastic large cell lymphoma (ALCL) is an aggressive non-Hodgkin lymphoma. It mostly invades lymph nodes with extranodal involvement observed in the soft tissue, bone, and skin.
PATIENT CONCERNS: We report a 34-year-old Chinese male patient who presented with headache, diplopia, and vomit. Cerebrospinal fluid (CSF) analysis via lumbar puncture showed elevated CSF pressure, elevated CSF protein concentrations, decreased CSF glucose and chloride concentration significantly, and pleocytosis of 68 to 350 × 10/L, in which lymphocytes and monocytes were predominant. These changes could be suggestive of tuberculous (TB) meningitis. Enhanced magnetic resonance imaging of spinal cord delineated multiple enhancing nodules in spinal cord, cauda equina, and cristae membrane, and multiple abnormal enhancing lesions in bilateral lumbar intervertebral foramen.
DIAGNOSES: Spinal dura mater biopsy and paraffin pathology examination revealed anaplastic lymphoma kinase positive ALCL.
INTERVENTIONS: High-dose methotrexate, cytosine arabinoside craniospinal, and radiotherapy.
OUTCOMES: Last follow-up on September 22, 2015 showed no evidence of tumor recurrence and the lower extremity muscle strength recovered to 4/5.
LESSONS: ALCL of primary central nervous system is an exceedingly rare tumor, which is usually misdiagnosed as meningitis (especially TB meningitis) according to clinical manifestation and laboratory examination. Thus closely monitoring patient's conditions and timely adjusting therapeutic regimen during treatment are necessary.

Related:

ALK

Kitahara H, Maruyama D, Maeshima AM, et al.
Prognosis of patients with peripheral T cell lymphoma who achieve complete response after CHOP/CHOP-like chemotherapy without autologous stem cell transplantation as an initial treatment.
Ann Hematol. 2017; 96(3):411-420 [PubMed] Related Publications

Cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP)/CHOP-like chemotherapy has been mostly applied to patients with untreated peripheral T cell lymphoma (PTCL). Because the long-term outcome of patients with PTCL, especially those achieving complete response (CR), has not been fully elucidated, we retrospectively analyzed 78 consecutive patients initially treated with CHOP/CHOP-like chemotherapy, without high-dose chemotherapy followed by autologous stem cell transplantation (HDC/auto-SCT). Median overall and progression-free survivals in all 78 patients were 44 and 17 months, respectively, with a median follow-up of 62 months. In the 53 patients achieving CR, the median relapse-free survival (RFS) was 21 months, and 2-, 3-, and 5-year RFSs were 46, 45, and 36%, respectively. Although our results showed an unfavorable outcome for PTCL as a whole, those who achieved CR following CHOP/CHOP-like chemotherapy did not always have a poor outcome without the consolidation of HDC/auto-SCT; in particular, 45% of the 65 years or younger patients were alive without disease at 5 years.

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