Kinase-positive Large B-cell Lymphoma Research Articles

Lorlatinib Induces Rapid and Durable Response in Refractory Anaplastic Lymphoma Kinase-Positive Large B-Cell Lymphoma.

Article Tools CASE REPORTS Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/PO.22.00536 JCO Precision Oncology no. 7 (2023) e2200536. Published online February 21, 2023. Lorlatinib Induces Rapid and Durable Response in Refractory Anaplastic Lymphoma Kinase–Positive Large B-Cell Lymphoma Baldeep Wirk , MD1xBaldeep WirkSearch for articles by this author; Jozef Malysz, MD1xJozef MalyszSearch for articles by this author; Esther Choi, MD1xEsther ChoiSearch for articles by this author; and Natthapol Songdej, MD1xNatthapol SongdejSearch for articles by this author Show More 1Penn State College of Medicine, Hershey, PA https://doi.org/10.1200/PO.22.00536 First Page Full Text PDF Figures and Tables © 2023 by American Society of Clinical OncologyPRIOR PRESENTATIONThe abstract of this manuscript was previously presented as a poster at the American Society of Transplantation & Cellular Therapy Meetings, Salt Lake City, UT, April 23-26, 2022.AUTHOR CONTRIBUTIONSConception and design: Baldeep Wirk, Jozef Malysz, Natthapol SongdejAdministrative support: Natthapol SongdejCollection and assembly of data: Baldeep Wirk, Jozef Malysz, Natthapol SongdejData analysis and interpretation: Baldeep Wirk, Jozef Malysz, Natthapol SongdejManuscript writing: All authorsFinal approval of manuscript: All authorsAccountable for all aspects of the work: All authorsAUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTERESTThe following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/po/author-center.Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open Payments).Natthapol SongdejConsulting or Advisory Role: Blueprint MedicinesNo other potential conflicts of interest were reported.

Anaplastic lymphoma kinase positive large B-cell lymphoma mimicking as plasma cell neoplasm: A rare case report

Anaplastic lymphoma kinase positive large B-cell lymphoma mimicking as plasma cell neoplasm: A rare case report

Frontiers in Bone, Soft Tissue, and Hematologic Pathology.

This special section of 6 articles includes the proceedings of the Seventh Princeton Integrated Pathology Symposium (PIPS): Bone, Soft Tissue and Hematologic Pathology, and other related reviews. The symposium was held virtually on Saturday, May 16, 2020. These reviews have numerous tables and figures, and may serve as a handy reference for your daily practice.Beginning Part I, to commemorate the late Juan Rosai, MD, Garcia and DiCarlo review the clinical, radiologic, and pathologic features of Rosai-Dorfman disease of bone and soft tissue. The authors discuss its differential diagnosis, pathogenesis, and current management. The diagnostic hallmarks are emperipolesis and S100-positive histiocytes. However, bone and soft tissue lesions tend to have a small number of characteristic histiocytes, less conspicuous emperipolesis and areas of fibrosis or storiform spindle cells, and can become a diagnostic challenge. The authors summarize the markers and genomic profiles of Rosai-Dorfman disease versus its differential diagnoses in a table.Advances in tumor genetics and markers propelled updates in the most recent edition of the World Health Organization classification of soft tissue and bone tumors. Wei and Siegal thus provide an overview on the current concepts of small round cell tumors of bone and soft tissue. They focus on salient histologic features, key immunophenotypic characteristics, and recent molecular genetic advancements of these small, round cell tumors. Several emerging entities are noteworthy for their unique molecular and clinical characteristics.Similar to the small, round cell tumors, some lesions of bone and soft tissue were historically classified as reactive, but are recently considered as neoplasms. They are clinically aggressive and have reproducible molecular signatures. Thus, these “reactive” lesions should be best classified and treated as neoplasms. A timely update by Memon, Wei, and Siegal on the subject addresses these evolving lesions, and will help meet the diagnostic challenges of these “reactive” yet aggressive lesions. Of note, molecular typing is often required to accurately diagnose these lesions.In Part II of this special section, we begin with the discussion of lymphoproliferative neoplasms with plasmablastic morphology that includes plasmablastic lymphoma, plasmablastic myeloma, primary effusion lymphoma, human herpesvirus 8–positive diffuse large B-cell lymphoma, and anaplastic lymphoma kinase–positive large B-cell lymphoma. They each have distinct morphologic and immunophenotypic characteristics. Here, Zhou and Nassiri not only thoroughly review the diagnostic criteria and tools, but provide a practical diagnostic algorithm for differentiating lymphoproliferative neoplasms with plasmablastic morphology.Many lymphoma and virally transformed lymphoproliferative disorders are positive for cluster of differentiate 30 (CD30). Given the low expression of CD30 in normal tissue, CD30 has been a subject of developing targeted therapy for decades. Schwarting et al share their first-hand experiences and knowledge as early investigators on CD30, present diagnostic pearls of common CD30-positive neoplasms, and provide perspectives on targeted therapies of CD30-positive hematological malignancies. As a humanized anti-CD30 antibody, brentuximab vedotin was approved in 2012 for treating refractory Hodgkin lymphoma and anaplastic large cell lymphoma. Additional therapies based on chimeric antigen receptor–T cells targeting CD30 are on the horizon. These therapies are also reviewed with updates from recent clinical trials.COVID-19 caused unprecedented socioeconomic and healthcare burdens throughout the world. Most COVID-19 research was focused on its impact on respiratory, cardiovascular, and coagulation systems. However, the hematologic complications of COVID-19 remain poorly understood. Because HIV and other viral pandemics have been associated with severe hematologic complications, the lessons learned from HIV and other viral pandemics may help us better understand those of COVID-19. Therefore, Karcher thoroughly reviews the hematologic complications of HIV and respiratory pandemics, including early data on those of COVID-19. The emerging knowledge in the hematologic complications of HIV, COVID-19, and other viral pandemics will greatly promote prevention, diagnosis, and treatment of hematologic complications in the future.We are grateful to former Archives Interim Editor-in-Chief, Donna Hansel, MD, PhD, and current Editor-in-Chief Alain Borczuk, MD, the other advisory committee members of the PIPS, the authors, and the reviewers. We also wish to thank Patrick Kearns, Katie Giesen, and Hilary Price at the Archives editorial office, James Demetriades, MBA, and Elliot A. Krauss, MD, at Princeton Medical Center, and F. Michael Walsh, MD, MBA, at Aurora Diagnostics. Without them, this special section would not be possible.

Anaplastic Lymphoma Kinase Positive Large B-cell Lymphoma Mimicking Metastatic Carcinoma of the Cervical Lymph Node from an Unknown Primary Lesion

Anaplastic lymphoma kinase positive large B-cell lymphoma (ALK+LBCL) is a rare subtype of B-cell lymphoma with aggressive features and a poor prognosis. The rarity of this disease and similarity of microscopic features with undifferentiated epithelial neoplasm disturb the provision of proper treatment. A 57-year-old male presented with a rapidly growing and painless mass on the left side of the neck. Metastatic carcinoma of an unknown primary (CUP) lesion was initially suspected based on the pathologic results obtained from a core needle biopsy, but it was finally diagnosed as ALK+LBCL after a modified radical neck dissection. We herein report a case of ALK+LBCL mimicking CUP with a literature review.

Anaplastic lymphoma kinase–positive large B-cell lymphoma: a case report with particular immunophenotypic features

Anaplastic lymphoma kinase-positive large B-cell lymphoma is a rare and aggressive B-cell lymphoma mostly associated with t(2:17) involving the clathrin gene at 17q23 and the anaplastic lymphoma kinase gene at 2p23. The characteristic immunophenotype includes a granular cytoplasmic anaplastic lymphoma kinase expression, CD20 negativity and the presence of plasma cell markers (CD138, VS38c, and CD38). We report a case with aberrant immunophenotype (CD138-, VS38c-, CD38+/-) and discuss the utility of other immunohistochemical markers in establishing a terminal B-cell differentiation.

Pediatric Anaplastic Lymphoma Kinase–Positive Large B-cell Lymphoma: A Case Report and Review of the Literature

We present a case of pediatric anaplastic lymphoma kinase-positive large B-cell lymphoma (ALK-positive LBCL) with a cervical, mesentery, and pelvis cavity mass. Histologic examination of the cervical mass revealed that the lesion was composed of diffuse large immunoblastic-like or plasmablastic-like tumor cells with a sinusoidal growth pattern. The tumor cells were strongly immunoreactive for ALK; revealed a granular cytoplasmic distribution; and were diffusely positive for CD45, CD4, CD138, epithelial membrane antigen, and multiple myeloma oncogene-1 but negative for CD20 and CD79a. The patient underwent 5 courses of cyclophosphamide, doxorubicin, vincristine, prednisone, and etoposid and obtained a remarkable clinical response with regression of mesentery and pelvis cavity mass. We suggest that this distinct subtype of large B-cell lymphoma should belong to the spectrum of pediatric lymphomas and that radiologic examination should be performed to inspect the progression of disease even if the patients experienced complete remission at initial chemotherapy.

ALK+ large B‐cell lymphoma: A rare variant of aggressive large B‐cell lymphoma mimicking carcinoma on cytology specimens

Anaplastic lymphoma kinase positive large B-cell lymphoma (ALK+ LBCL) was recognized as a distinct entity by the 2008 WHO classification of lymphomas. Histologically, the tumor cells exhibit either plasmablastic or immunoblastic morphology, with characteristic granular staining for ALK. The purpose of this study is to evaluate the cytologic findings of ALK+ LBCL. The cytologic material obtained by needle biopsy from three cases of ALK+ LBCL was evaluated. All lesions were nodal and the cytologic material analyzed included air-dried and alcohol-fixed slides stained with modified Giemsa and/or HE stains. The following morphologic criteria were assessed: cellularity, cluster characteristics, cell size, cytoplasmic and nuclear characteristics, and background composition. The cytology specimens obtained from the needle biopsies were moderately to highly cellular and composed of a population of large cells with immunoblastic or plasmablastic morphology. Single cells were present in all three cases, but two cases also showed the presence of clusters with acinar and papillary architecture. Multinucleation was noted in all three cases. Amorphous metachromatic background material was noted focally in the modified Giemsa stained slides in all three cases. Immunostains performed on cytology specimens showed cytoplasmic immunoreactivity for ALK, with characteristic granular features. ALK+ LBCL is a rare recently recognized type of lymphoma with unique morphologic and immunophenotypic findings that can mimic epithelial tumors. Recognition of this potential diagnostic pitfall is critical to prevent unnecessary additional work-up and mistreatment.

Anaplastic Lymphoma Kinase–Positive Large B-Cell Lymphoma

Anaplastic Lymphoma Kinase–Positive Large B-Cell Lymphoma

Anaplastic lymphoma kinase–positive large B-cell lymphoma with complex karyotype and novel ALK gene rearrangements

Anaplastic lymphoma kinase-positive large B-cell lymphoma is a rare non-Hodgkin lymphoma that exhibits a characteristic immunoblastic/plasmablastic morphology and is frequently associated with t(2;17)(p23;q23) and expression of Clathrin-anaplastic lymphoma kinase fusion protein. Here, we report a refractory anaplastic lymphoma kinase-positive large B-cell lymphoma in a 49-year-old human immunodeficiency virus-positive man. The neoplastic cells expressed CD138, epithelial membrane antigen, CD45, and perforin, and showed a strong granular cytoplasmic anaplastic lymphoma kinase staining pattern. Conventional chromosome analysis revealed a clone with multiple anomalies and a chromosome count of 76 to 79. Fluorescence in situ hybridization studies showed 5 copies of the ALK gene with 2 intact signals and 3 signals resulting from 2 independent, previously unreported, rearrangements. One rearrangement, seen in 2 copies, involved translocation of ALK sequences to chromosome Xq21. The second rearrangement involved translocation of ALK sequences to chromosome 12q24.1. This case broadens the cytogenetic alterations in anaplastic lymphoma kinase-positive large B-cell lymphoma, and it also demonstrates the high genetic instability of this tumor.

ALK-postive Large B-cell Lymphoma: Report of Two Cases and Review of the Literature

Summary Anaplastic lymphoma kinase positive large B-cell lymphoma (ALK+ LBCL) is a rare variant of large B-cell lymphoma, but it rarely expresses B-lineage antigens (e.g CD20, CD79a) while showing an abnormal immunophenotype, such as positive for ALK, EMA, CD38, CD138. Only 55 cases of ALK+ LBCL have been reported so far in the published literature [1]. We present two additional cases of ALK+ LBCL, which were sent to our department for consultation from other hospitals. One was initially diagnosed as metastatic poorly differentiated carcinoma and the other was not able to be diagnosed. The two cases were finally diagnosed as “ALK+ LBCL” at our department of pathology (see below). The chemotherapy with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) was given, respectively. Case 1 was given radiation therapy after chemotherapy, and case 2 wasn’t. Case 1, followed up for 16 months, was free of disease. Case 2 died at 8 months after the diagnosis. Due to the abnormal immunophenotype and rareness, the diagnosis of ALK+ LBCL is often difficult, even being misdiagnosed as carcinoma or plasma cell neoplasm. However, the treatment for these diseases is quite different from each another. Avoiding misdiagnosis of ALK+ LBCL is of great clinic importance. In this report, we describe the clinical, morphological, immunohistiochemical and cytogenetic features of the two ALK+ LBCL cases, reviewed 55 published cases, and compared the features with those of literature-reported cases. We came to the conclusions: ALK+ LBCL could affect non-adult and adult with a bimodal age distribution, with an average age of 12.5 years in the non-adult, and 43.5 years in the adult. ALK+ LBCL is a potential diagnostic pitfall for pathologists. Its diagnosis clues are that neoplastic cells are immunoblastic or/and plasmacytoid with prominent central nucleoli, positive for ALK, EMA and some markers of late (plasma cell-like) B-cell differentiation, like CD138, VS38 and immunoglobulins, negative for B-cell markers like CD20 and CD79a.  The investigation of involved genetic abnormality (CLTC-ALK fusion, or NPM-ALK rearrangement) contributes to confirm ALK+ LBCL. ALK+ LBCL has highly aggressive biobehavior and poor response to standard therapies. More patient case collection and prospective studies are needed.