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2033 Multicentric Hyaline-Vascular Castleman Disease: The Missing Link?

Program: Oral and Poster Abstracts
Session: 654. MGUS, Amyloidosis and Other Non-Myeloma Plasma Cell Dyscrasias: Clinical and Epidemiological: Poster I
Hematology Disease Topics & Pathways:
Clinical Practice (Health Services and Quality), Plasma Cell Disorders, Diseases, Immune Disorders, Lymphoid Malignancies
Saturday, December 9, 2023, 5:30 PM-7:30 PM

Maxime Beydon1*, Yannick Dieudonné2*, Veronique Meignin, MD3*, Eléonore Kaphan, MD4*, Louis Terriou, M.D5*, Jean Philippe Martellosio6*, Jean-Francois Viallard, MD PhD7*, Claire Ballot-Schmit8*, Marie Emilie Dourthe, MD, PhD9*, Coralie Mallebranche, MD10*, Deborah Meyran, MD11*, Lucas Maisonobe12*, Lionel Galicier13*, Eric Oksenhendler13* and David Boutboul, MD, PhD14*

1Hôpital Saint-Louis, Paris, France
2Strasbourg University Hospital, Strasbourg, FRA
3Pathology, Hopital Saint-Louis, PARIS, FRA
4Saint-Louis Hospital, Paris, FRA
5CHU Lille, Université de Lille, Lille, France
6Poitiers University Hospital, Poitiers, France
7Service Médecine Interne, Haut-Leveque Hospital, Pessac, France
8Hopital Jean Minjoz, Besançon, France
9Department of Pediatric Hematology, Robert Debré Hospital, AP-HP, Université Paris Cité, Paris, France., Paris, France
10immuno-hemato-oncology Unit, Univ Angers, Nantes Université, Inserm, CNRS, CRCI2NA, SFR ICAT, CHU Angers,, Angers, FRA
11Hopital Robert Debré, Paris, France
12Hopital Bichat, Paris, France
13Service d'Immunopathologie Clinique, Saint Louis hospital, AP-HP, Paris, France
14Service d'Immunopathologie Clinique, Saint Louis hospital, AP-HP, Paris, Paris, France

Introduction: Castleman disease (CD) is a rare lymphoproliferative disorder that encompasses distinct clinicopathological entities. Unicentric form of the disease (UCD) usually involves a single lymph node station, exhibits hyaline vascular (HV) pathological changes with follicular dendritic cell expansion, and may associate with specific and life-threatening complications including paraneoplastic pemphigus (PNP) and follicular dendritic cell sarcoma (FDCS). Plasma cell interfollicular infiltration is absent in the HV subtype as opposed to the Plasma-Cell (PC) or Mixed subtypes. PC subtype has been associated with inflammatory symptoms thought to be secondary to plasma cell infiltration and represents the majority of HHV8-negative “idiopathic” multicentric forms of the disease. Interestingly, patients with PC-UCD behave as PC-MCD, suggesting a stronger role of histology rather than Unicentric vs Multicentric phenotype in disease expression. We here studied the phenotype of HV-MCD, a rare subtype of CD characterized by hyaline-vascular pathological changes involving 2 or more lymph node stations.

Methods: Patients were screened through the French national reference center for CD between January 1994 and June 2023. Cases were followed from first symptoms to last follow-up visit. Comparators consisted of patients with HV-UCD and patients with PC/Mixed iMCD (P/M-iMCD). All cases and biopsies were reviewed by three expert clinicians and one expert pathologist.

Results: Sixteen patients with a diagnosis of HHV8-negative HV-MCD were identified. All patients had supra- and infradiaphragmatic involvement. Four were excluded because of a subsequent diagnosis of POEMS, systemic lupus erythematosus, tuberculosis, or inborn error of immunity. The 12 remaining patients were considered as having HV-iMCD and compared to 101 patients with P/M-iMCD and 139 patients with HV-UCD. Characteristics and comparison between the 3 groups are depicted in Table 1.

When compared to HV-UCD, HV-iMCD displayed frequent systemic involvement with significantly higher ECOG, higher frequency of fever and splenomegaly, and higher levels of C-reactive protein, gammaglobulins, leukocytes and ferritinemia (Figure 1). Age at diagnosis was not different between HV-UCD and HV-iMCD. No cases of TAFRO syndrome were observed in HV-UCD whereas 4 cases were observed in HV-iMCD. All cases of PNP (n=12) and FDCS (n=3) were observed in the HV-UCD group.

We observed a younger age at diagnosis in HV-iMCD compared to P/M-iMCD (median 24 [range 13-70] vs median 50 [range 11-88] years respectively, p = 0.01). We also noted a trend towards lower levels of C reactive protein and gammaglobulins as well a higher albumin level in HV-iMCD vs P/M-iMCD but these differences were not significant (Figure 1 and Table 1).

Treatments were similar between HV-iMCD and P/M-iMCD with prescription of steroids or anti-IL6R as first line therapy in 8/12 (67%) and 61/101 (60%) respectively. As expected, surgery was the first line therapy in 98/139 (72%) of HV-UCD patients. One patient with HV-iMCD and two with HV-UCD died (logrank p = 0.10), whereas 13 died in the P/M-iMCD group (logrank p = 0.8).

Conclusions: These data altogether indicate that HV-iMCD appears to be a distinct entity in CD landscape, sharing pathological aspects of HV-UCD and clinical/biological features of P/M iMCD. In line with this view, there seems to be no overlap between HV-UCD and HV-iMCD-related complications. The findings also suggest that nodal PC infiltration is not sufficient to explain the inflammatory pattern of iMCD.

Disclosures: Meignin: EUSAPHARMA: Consultancy. Terriou: Alexion: Honoraria; Sobi: Honoraria; Eusapharma: Consultancy. Viallard: EUSAPHARMA: Consultancy. Galicier: EUSAPHARMA: Consultancy; AMGEN: Consultancy. Oksenhendler: EusaPharma: Consultancy; CSL Behring: Consultancy.

*signifies non-member of ASH