Plasmablastic lymphoma (PBL) is an aggressive lymphoma commonly associated with HIV infection. However, PBL can also be seen in patients with other immunodeficiencies as well as in immunocompetent ...individuals. Because of its distinct clinical and pathological features, such as lack of expression of CD20, plasmablastic morphology, and clinical course characterized by early relapses and subsequent chemotherapy resistance, PBL can represent a diagnostic and therapeutic challenge for pathologists and clinicians alike. Despite the recent advances in the therapy of HIV-associated and aggressive lymphomas, patients with PBL for the most part have poor outcomes. The objectives of this review are to summarize the current knowledge on the epidemiology, biology, clinical and pathological characteristics, differential diagnosis, therapy, prognostic factors, outcomes, and potential novel therapeutic approaches in patients with PBL and also to increase the awareness toward PBL in the medical community.
Hepatosplenic T-cell lymphoma (HSTCL) is a rare and clinically aggressive type of T-cell lymphoma that arises most often in adolescents and young adults. Patients with HSTCL commonly present with ...B-symptoms and cytopenias, which may suggest a diagnosis of acute leukemia initially. Patients present with extranodal disease involving the spleen, liver and bone marrow; lymphadenopathy is usually absent. The lymphoma cells can show a spectrum of cell sizes and are of T-cell lineage, often negative for CD4 and CD8 and positive for T-cell receptor γδ or, less often, αβ. Recent studies have identified gene mutations in oncogenic pathways that are likely involved in pathogenesis and may be targets for therapy. Mutations in STAT3 or STAT5B lead to activation of the JAK/STAT pathway, and mutations involving SETD2, IN080 and ARID1 are involved in chromatin modification. Currently, there is no consensus standard of care for HSTCL patients, although several studies support a role for allogeneic hematopoietic stem cell transplant. Although patients with HSTCL are best treated in the context of clinical trials, the rarity of these neoplasms likely necessitates a multi-institutional approach. In this review, we focus on the clinicopathologic and genetic characteristics of HSTCL. We also discuss the differential diagnosis and therapeutic approaches.
•Hepatosplenic T-cell lymphoma (HSTCL) is a rare and aggressive T-cell lymphoma.•Patients commonly present with B symptoms and splenomegaly.•Lymphadenopathy is uncommon, and diagnosis can be challenging.•There has been substantial progress in understanding the pathogenesis of HSTCL.•This progress has the potential to facilitate improvement of patient management.
LEARNING OBJECTIVES:After reading this article, the participant should be able to1. Describe the diagnostic criteria for breast implant–associated (BIA) anaplastic large cell lymphoma (ALCL). 2. ...Appropriately evaluate a patient with suspected BIA-ALCL, including appropriate imaging, laboratory tests, and pathologic evaluation. 3. Understand the operative treatment of BIA-ALCL, and indications for systemic chemotherapy and/or radiation therapy in advanced disease. 4. Understand treatment outcomes and prognosis based on stage of disease.
SUMMARY:The goal of this continuing medical education module is to present the assessment of a patient with suspected breast implant–associated anaplastic large cell lymphoma, the evaluation and diagnosis, the preoperative oncologic workup, the formation and execution of a surgical treatment plan, and the inclusion of adjunct treatments when indicated. In addition, staging and disease progression for treatment of breast implant–associated anaplastic large cell lymphoma are discussed.
Breast implant-associated anaplastic large-cell lymphoma (ALCL) is a recently described clinicopathologic entity that usually presents as an effusion-associated fibrous capsule surrounding an ...implant. Less frequently, it presents as a mass. The natural history of this disease and long-term outcomes are unknown.
We reviewed the literature for all published cases of breast implant-associated ALCL from 1997 to December 2012 and contacted corresponding authors to update clinical follow-up.
The median overall survival (OS) for 60 patients was 12 years (median follow-up, 2 years; range, 0-14 years). Capsulectomy and implant removal was performed on 56 of 60 patients (93%). Therapeutic data were available for 55 patients: 39 patients (78%) received systemic chemotherapy, and of the 16 patients (28%) who did not receive chemotherapy, 12 patients opted for watchful waiting and four patients received radiation therapy alone. Thirty-nine (93%) of 42 patients with disease confined by the fibrous capsule achieved complete remission, compared with complete remission in 13 (72%) of 18 patients with a tumor mass. Patients with a breast mass had worse OS and progression-free survival (PFS; P = .052 and P = .03, respectively). The OS or PFS were similar between patients who received and did not receive chemotherapy (P = .44 and P = .28, respectively).
Most patients with breast implant-associated ALCL who had disease confined within the fibrous capsule achieved complete remission. Proper management for these patients may be limited to capsulectomy and implant removal. Patients who present with a mass have a more aggressive clinical course that may be fatal, justifying cytotoxic chemotherapy in addition to removal of implants.
In this review, we focus on the current understanding of the diagnosis of human herpesvirus 8 (HHV8)-associated lymphoproliferative disorders-a group of entities that range from hyperplastic ...proliferations to frank lymphomas. These diseases tend to occur in immunodeficient patients, but may occur in immunocompetent individuals as well. In recent years, we have learned of occasional cases with overlapping features among HHV8 entities, such as lesions intermediate between primary effusion lymphoma and HHV8-positive diffuse large B-cell lymphoma, not otherwise specified or cases sharing features of multicentric Castleman disease and germinotropic lymphoproliferative disorder. There is also a significant clinical overlap between these entities. It is important to have a better understanding of the biology of these lesions and to refine diagnostic criteria of these lesions, as the use of immunosuppressive agents to treat a variety of diseases, the expanded use of transplant as a therapeutic modality for a variety of cancers and organ failure patients, and the extended longevity of HIV-positive patients will likely result in an increased incidence of these lymphoproliferative processes in the future.
Diffuse large B-cell lymphoma (DLBCL) is stratified into prognostically favorable germinal center B-cell (GCB)–like and unfavorable activated B-cell (ABC)–like subtypes based on gene expression ...signatures. In this study, we analyzed 893 de novo DLBCL patients treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). We show that MYC/BCL2 protein coexpression occurred significantly more commonly in the ABC subtype. Patients with the ABC or GCB subtype of DLBCL had similar prognoses with MYC/BCL2 coexpression and without MYC/BCL2 coexpression. Consistent with the notion that the prognostic difference between the 2 subtypes is attributable to MYC/BCL2 coexpression, there is no difference in gene expression signatures between the 2 subtypes in the absence of MYC/BCL2 coexpression. DLBCL with MYC/BCL2 coexpression demonstrated a signature of marked downregulation of genes encoding extracellular matrix proteins, those involving matrix deposition/remodeling and cell adhesion, and upregulation of proliferation-associated genes. We conclude that MYC/BCL2 coexpression in DLBCL is associated with an aggressive clinical course, is more common in the ABC subtype, and contributes to the overall inferior prognosis of patients with ABC-DLBCL. In conclusion, the data suggest that MYC/BCL2 coexpression, rather than cell-of-origin classification, is a better predictor of prognosis in patients with DLBCL treated with R-CHOP.
•DLBCL patients with MYC/BCL2 coexpression demonstrate inferior prognosis and high-risk gene expression signatures.
Castleman disease (CD) comprises 3 poorly understood lymphoproliferative variants sharing several common histopathological features. Unicentric CD (UCD) is localized to a single region of lymph ...nodes. Multicentric CD (MCD) manifests with systemic inflammatory symptoms and organ dysfunction due to cytokine dysregulation and involves multiple lymph node regions. Human herpesvirus 8 (HHV-8) causes MCD (HHV-8–associated MCD) in immunocompromised individuals, such as HIV-infected patients. However, >50% of MCD cases are HIV and HHV-8 negative (defined as idiopathic iMCD). The clinical and biological behavior of CD remains poorly elucidated. Here, we analyzed the clinicopathologic features of 74 patients (43 with UCD and 31 with iMCD) and therapeutic response of 96 patients (43 with UCD and 53 with iMCD) with HIV-/HHV-8–negative CD compared with 51 HIV-/HHV-8–positive patients. Systemic inflammatory symptoms and elevated inflammatory factors were more common in iMCD patients than UCD patients. Abnormal bone marrow features were more frequent in iMCD (77.0%) than UCD (45%); the most frequent was plasmacytosis, which was seen in 3% to 30.4% of marrow cells. In the lymph nodes, higher numbers of CD3+ lymphocytes (median, 58.88 ± 20.57) and lower frequency of CD19+/CD5+ (median, 5.88 ± 6.52) were observed in iMCD patients compared with UCD patients (median CD3+ cells, 43.19 ± 17.37; median CD19+/CD5+ cells, 17.37 ± 15.80). Complete surgical resection is a better option for patients with UCD. Siltuximab had a greater proportion of complete responses and longer progression-free survival (PFS) for iMCD than rituximab. Centricity, histopathological type, and anemia significantly impacted PFS. This study reveals that CD represents a heterogeneous group of diseases with differential immunophenotypic profiling and treatment response.
•HIV-negative UCD and iMCD are heterogeneous at the clinical, immunophenotypic, and pathologic levels.•Complete surgical resection is the primary option of treatment of UCD, while siltuximab is more effective for iMCD than rituximab.
Breast implant–associated anaplastic large-cell lymphoma (BIA-ALCL) is a CD30-positive, anaplastic lymphoma kinase–negative T-cell lymphoma. Nearly all cases have been associated with textured ...implants. Most cases are of effusion-limited, indolent disease, with an excellent prognosis after implant and capsule removal. However, capsular invasion and tumor mass have a more aggressive course and a fatal outcome risk. This review summarizes the current knowledge on BIA-ALCL cell of origin and immunologic factors underlying its pathogenesis. Cytokine expression profiling of BIA-ALCL cell lines and clinical specimens reveals a predominantly type 17 helper T-cell (Th17)/Th1 signature, implicating this as its cell of origin. However, a Th2 allergic inflammatory response is suggested by the presence of IL-13, with infiltration of eosinophils and IgE-coated mast cells in clinical specimens of BIA-ALCL. The microenvironment-induced T-cell plasticity, a factor increasingly appreciated, may partially explain these divergent results. Mutations resulting in constitutive Janus kinase (JAK)–STAT activation have been detected and associated with BIA-ALCL pathogenesis in a small number of cases. One possible scenario is that an inflammatory microenvironment stimulates an immune response, followed by polyclonal expansion of Th17/Th1 cell subsets with release of inflammatory cytokines and chemokines and accumulation of seroma. JAK-STAT3 gain-of-function mutations within this pathway and others may subsequently lead to monoclonal T-cell proliferation and clinical BIA-ALCL. Current research suggests that therapies targeting JAK proteins warrant investigation in BIA-ALCL.
Breast implant-associated anaplastic large cell lymphoma (ALCL) is a distinctive type of T-cell lymphoma that arises around breast implants. Although rare, all cases with adequate history have ...involved a textured breast implant. The objective of this study was to determine the U.S. incidence and lifetime prevalence of breast implant-associated ALCL in women with textured breast implants.
This is a retrospective review of documented cases of breast implant-associated ALCL in the United States from 1996 to 2015. The incidence and prevalence were determined based on a literature and institutional database review of breast implant-associated ALCL cases and textured breast implant sales figures from implant manufacturers' annualized data.
One hundred pathologically confirmed breast implant-associated ALCL cases were identified in the United States. Mean age at diagnosis was 53.2 ± 12.3 years. Mean interval from implant placement to diagnosis was 10.7 ± 4.6 years. Forty-nine patients had breast implants placed for cosmetic reasons, 44 for mastectomy reconstruction, and seven for unknown reasons. Assuming that breast implant-associated ALCL occurs only in textured breast implants, the incidence rate is 2.03 per 1 million person-years (203 per 100 million person-years), which is 67.6 times higher than that of primary ALCL of the breast in the general population (three per 100 million per year; p < 0.001). Lifetime prevalence was 33 per 1 million persons with textured breast implants.
This study demonstrates a statistically significant association between textured breast implants and breast implant-associated ALCL. Although women with a textured breast implant have a low risk of developing breast implant-associated ALCL, the current U.S. incidence is significantly higher than that of primary ALCL of the breast in the general population.
Breast implant-associated anaplastic large cell lymphoma is a newly recognized provisional entity in the 2017 revision of the World Health Organization Classification of Tumors of Hematopoietic and ...Lymphoid Tissues. It is an uncommon, slow growing T-cell lymphoma with morphology and immunophenotype similar to anaplastic lymphoma kinase-negative anaplastic large cell lymphoma. However, the presentation and treatment are unique. Breast implant-associated anaplastic large cell lymphoma often presents as a unilateral effusion confined to the capsule of a textured-surface breast implant, a median time of 9 years after the initial implants have been placed. Although it follows an indolent clinical course, breast implant-associated anaplastic large cell lymphoma has the potential to form a mass, to invade locally through the capsule into breast parenchyma or soft tissue and/or to spread to regional lymph nodes. In most cases, an explantation with a complete capsulectomy removing all disease, without chemotherapy is considered to be curative and confers an excellent event free and overall survival. Here we provide a comprehensive review of breast implant-associated anaplastic large cell lymphoma, including history, epidemiology, clinical features, imaging and pathology findings, pathologic handling, pathogenic mechanisms, model for progression, therapy and outcomes as well as an analysis of causality between breast implants and anaplastic large cell lymphoma.
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