Progression of Hodgkin Lymphoma and Plasma Cell Neoplasms

Report From the 2021 SH/EAHP Workshop

Reza Nejati, MD; Catalina Amador, MD; Magdalena Czader, MD, PhD; Elizabeth Thacker; Devang Thakkar; Sandeep S. Dave, MD; Ahmet Dogan, MD, PhD; Amy Duffield, MD, PhD; John R. Goodlad, MBChB, MD; German Ott, MD; Mariusz A. Wasik MD; Wenbin Xiao, MD, PhD; James R. Cook, MD, PhD

Disclosures

Am J Clin Pathol. 2023;159(6):598-613.

Abstract and Introduction

Abstract

Objectives: To summarize cases submitted to the 2021 Society for Hematopathology/European Association for Haematopathology Workshop under the categories of progression of Hodgkin lymphoma, plasmablastic myeloma, and plasma cell myeloma.

Methods: The workshop panel reviewed 20 cases covered in this session. In addition, whole-exome sequencing (WES) and whole-genome RNA expression analysis were performed on 10 submitted cases, including 6 Hodgkin lymphoma and 4 plasma neoplasm cases.

Results: The cases of Hodgkin lymphoma included transformed cases to or from various types of B-cell lymphoma with 1 exception, which had T-cell differentiation. The cases of plasma cell neoplasms included cases with plasmablastic progression, progression to plasma cell leukemia, and secondary B-lymphoblastic leukemia. Gene variants identified by WES included some known to be recurrent in Hodgkin lymphoma and plasma cell neoplasm. All submitted Hodgkin lymphoma samples showed 1 or more of these mutations: SOCS1, FGFR2, KMT2D, RIT1, SPEN, STAT6, TET2, TNFAIP3, and ZNF217.

Conclusions: Better molecular characterization of both of these neoplasms and mechanisms of progression will help us to better understand mechanisms of progression and perhaps develop better prognostic models, as well as identifying novel therapeutic targets.

Introduction

Session 6 of the 2021 Society for Hematopathology/European Association for Haematopathology Workshop was devoted to progression of Hodgkin lymphoma, plasmablastic myeloma, and plasma cell myeloma. A total of 20 cases were discussed in this session, including 6 cases that were presented orally by the submitters. The panel came to a consensus diagnosis on each case based on the available clinical information, morphology, immunophenotype, and, in many cases, molecular and clonality studies. In addition, whole-exome sequencing (WES) and whole-genome RNA expression analysis were performed on half of the submitted cases: 6 of Hodgkin lymphoma and 4 of plasma neoplasm. By summarizing the findings in the submitted cases, we hope to expand our understanding of clinical and morphologic presentations of transformation in these neoplasms and shed a light on molecular mechanisms of the pathogenesis and transformation of these B-cell lymphoid neoplasms.

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Table 1. Summary of the Submitted Classic Hodgkin Lymphoma Cases
Case No.	Submitter	Institution	Age, y	Sex	Panel diagnosis
Case No.	Submitter	Institution	Age, y	Sex	Initial	Progression/transformation
80	Dr Hu	The University of Texas Health Science Center at Houston	86	F	cHL	DLBCL
275	Dr Napier	Belfast Trust, Northern Ireland, UK	24	M	cHL	DLBCL
148	Dr Makarenko	Massachusetts General Hospital	43	M	cHL	DLBCL
114	Dr Sahin	Thomas Jefferson University Hospital	28	M	cHL	DLBCL
260	Dr Aypar	Memorial Sloan Kettering Cancer Center	35	F	GZL	cHL
265	Dr Singh	Stanford University School of Medicine	14	M	cHL	GZL
158	Dr Bruneau	Necker–Enfants Malades Hospital, France	67	F	cHL	ALCL, ALK negative
94	Dr Chekol	University of Pennsylvania, Philadelphia	74	M	Clonally related composite lymphoma (follicular lymphoma and classic Hodgkin lymphoma)

ALCL, anaplastic large cell lymphoma; cHL, classic Hodgkin lymphoma; DLBCL, diffuse large B-cell lymphoma; GZL, gray zone lymphoma.

Table 2. Summary of the Submitted NLPHL Cases
Case No.	Submitter	Institution	Age, y	Sex	Panel diagnosis
Case No.	Submitter	Institution	Age, y	Sex	Initial	Progression/transformation
88	Dr Molina	APHP, Necker, University of Paris, France	19	M	NLPHL	THRLBCL
191	Dr Sethi	Memorial Sloan Kettering Cancer Center	75	F	NLPHL	THRLBCL-like progression
146	Dr Mallick	All India Institute of Medical Sciences, India	33	M	NLPHL	DLBCL
118	Dr Cannatella	University of Nebraska Medical Center	34	M	NLPHL	NLPHL with altered phenotype posttreatment

DLBCL, diffuse large B-cell lymphoma; NLPHL, nodular lymphocyte-predominant Hodgkin lymphoma; THRLBCL, T-cell/histiocyte-rich large B-cell lymphoma.

Table 3. Summary of the Submitted Plasma Cell Neoplasm Cases
Case No.	Submitter	Institution	Age, y	Sex	Panel diagnosis
Case No.	Submitter	Institution	Age, y	Sex	Initial	Progression/transformation
186	Dr Liu	Memorial Sloan Kettering Cancer Center	52	F	PCM	PCM with plasmablastic progression
246	Dr Padilla	Texas Tech Health Science Center–El Paso	55	F	PCM	PCM with plasmablastic progression
205	Dr Khattar	Icahn School of Medicine at Mount Sinai	45	F	PCM with plasmablastic/anaplastic features
190	Dr Nakashima	Cleveland Clinic, USA	65	F	PCM	Plasma cell leukemia
18	Dr Yang	University of Minnesota	60	M	PCM	Secondary B-lymphoblastic leukemia
238	Dr Khattar	Icahn School of Medicine at Mount Sinai	63	F	PCM with aberrant CD3 expression
208	Dr Judd	University of New Mexico	65	M	PCN involving extramedullary site (stomach)
233	Dr Khattar	Icahn School of Medicine at Mount Sinai	61	M	PCN involving extramedullary site (testis)

PCM, plasma cell myeloma; PCN, plasma cell neoplasm.

Table 4. Summary of the Mutations in the Submitted Plasma Cell Neoplasm Cases
Gene	Pathway/function
KRAS	MAPK signaling
NRAS	MAPK signaling
BCL10	NF- κB signaling
KM2TD	Chromatin modification
KM2TA	Chromatin modification
IDH2	An enzyme for cellular respiration in the tricarboxylic acid
KLHL6	B-cell development
PTPN13	Phosphatase function
LTK	Receptor tyrosine kinase
ELL	Regulates small nuclear RNA transcription
MERTK	Receptor tyrosine kinase
APC	Tumor suppressor in Wnt signaling pathway
NRG1	Cell adhesion protein
RNF213	E3 ubiquitin-protein ligase