Flow cytometry characterization in central nervous system and pleural effusion multiple myeloma infiltration: an Italian national cancer institute experience

Marchesi, Francesco; Masi, Sara De; Summa, Valentina; Gumenyuk, Svitlana; Merola, Roberta; Orlandi, Giulia; Cigliana, Giovanni; Palombi, Francesca; Pisani, Francesco; Romano, Atelda; Spadea, Antonio; Papa, Elena; Canfora, Marco; Bellis, Francesco De; Conti, Laura; Mengarelli, Andrea; Cordone, Iole

doi:10.1111/bjh.13549

Cited by 11 publications

(9 citation statements)

References 10 publications

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“…A fourth patient treated for aggressive refractory PCM experienced a rapid rebound of M-protein within 4 weeks. Interestingly, there were no significant differences between the PCM immunophenotype assessed at diagnosis or relapse except for CD28 expression in three of the four relapsed cases (data not shown), as was also recently demonstrated by the Italian National Cancer Institute (Marchesi et al, 2015).…”

Section: á3-8á0 (Median 0á9) Disease Duration (Years) 1á2-7á1 (Mediasupporting

confidence: 80%

Aggressive and extramedullary plasma cell myeloma evade bone marrow flow cytometric minimal residual disease detection

et al. 2015

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We were interested to read the recent publication by Weinstock and colleagues (Weinstock et al, 2015), which described the incidence and clinical features of 55 cases of biopsy-proven extramedullary multiple myeloma, derived from a large cohort of consecutive patients who underwent stem cell transplantation, noting that the majority of this uncommon manifestation occurred at relapse. These findings were of particular interest to us as we recently collected data from patients undergoing minimal residual disease (MRD) assessment for plasma cell myeloma (PCM) by flow cytometry (FC), and focused our attention on those for whom disease was undetectable in the bone marrow (BM) but present elsewhere, and also found, with smaller numbers, that extramedullary disease (EMD) was more often the reason for a 'false 20* S, HDT, I (patient 6) 3 I, P, HDT (patient 4) 3 S, I, HDAC (patient 5) 1 P 1 S, HDT x 2, I 2 S, HDT 2 S, HDT, P 1 S, HDT, I, P (patient 8) 1 S, HDT x 2, I, P (patient 7) 3 S, HDT, I, P, HDAC 3 S, HDT x 2, I, P, HDAC 1 S, HDT, I, P, Ex, Ex 1 *Uniformly treated (N = 16); ISS, International Staging System; S, standard therapy (corticosteroid and conventional cytotoxic chemotherapy); I, immunomodulatory (thalidomide or lenalidomide); HDT, high dose therapy (melphalan/autologous stem cell transplant with cyclophosphamide stem cell mobilization); HDAC, histone deacetylase inhibitor; P, proteasome inhibitor; Ex, experimental agent.

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Section: á3-8á0 (Median 0á9) Disease Duration (Years) 1á2-7á1 (Mediasupporting

confidence: 80%

Aggressive and extramedullary plasma cell myeloma evade bone marrow flow cytometric minimal residual disease detection

et al. 2015

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“…We have recently documented that FCM can discriminate between reactive and neoplastic plasma cells in CSF samples with very low cell counts, confirming to be significantly more sensitive than standard approaches [21]. CSF FCM was performed on 5 out of 18 PCNSL cases and, despite the low cell count, a clonal B cell population was identified in one case.…”

Section: Discussionmentioning

confidence: 99%

Brain stereotactic biopsy flow cytometry for central nervous system lymphoma characterization: advantages and pitfalls

Cordone¹,

Masi²,

Carosi³

et al. 2016

J Exp Clin Cancer Res

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BackgroundBrain stereotactic biopsy (SB) followed by conventional histopathology and immunohistochemistry (IHC) is the gold standard approach for primary central nervous system lymphoma (PCNSL) diagnosis. Flow cytometry (FCM) characterization of fine-needle aspiration cytology and core needle biopsies are increasingly utilized to diagnose lymphomas however, no biological data have been published on FCM characterization of fresh single cell suspension from PCNSL SB. The aim of this study was to establish the feasibility and utility of FCM for the diagnosis and characterization of brain lymphomas from a tissue samples obtained by a single SB disaggregation.MethodsTwenty-nine patients with a magnetic resonance suggestive for PCNSL entered the study. A median of 6 SB were performed for each patient. A cell suspension generated from manual tissue disaggregation of a single, unfixed, brain SB, was characterized by FCM. The FCM versus standard approach was prospectively compared.ResultsFCM and IHC showed an high degree of agreement (89 %) in brain lymphoma identification. By FCM, 16 out of 18 PCNSL were identified within 2 h from biopsy. All were of B cell type, with a heterogeneous CD20 mean fluorescence intensity (MFI), CD10 positive in 3 cases (19 %) with surface Ig light chain restriction documented in 11 cases (69 %). No false positive lymphomas cases were observed. Up to 38 % of the brain leukocyte population consisted of CD8 reactive T cells, in contrast with the CD4 positive lymphocytes of the peripheral blood samples (P < 0.001). By histopathology, 18 B-PCNSL, only one CD10 positive (5 %), 1 primitive neuroectodermal tumor (PNET) and 10 gliomas were diagnosed. A median of 6 days was required for IHC diagnosis.ConclusionComplementary to histopathology FCM can contribute to a better characterization of PCNSL, although necrosis and previous steroid treatment can represent a pitfall of this approach. A single brain SB is a valid source for accurate FCM characterization of both lymphoma and reactive lymphocyte population, routinely applicable for antigen intensity quantification and consistently documenting an active mechanism of reactive CD8 T-lymphocytes migration in brain lymphomas. Moreover, FCM confirmed to be more sensitive than IHC for the identification of selected markers.

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“…Body cavity effusions occurring in the setting of plasma cell myelomas are not common (∼6% of cases), and they are nonneoplastic (nonmyelomatous) in most cases due to congestive heart disease or kidney insufficiency, liver dysfunction (cirrhosis, hypoalbuminemia), or inflammation/infection [18,34,35,36]. Rarely (in less than 1% of cases) a myelomatous infiltration of serous membranes may be the cause of fluid accumulation (fig.…”

Section: Plasma Cell Neoplasmsmentioning

confidence: 99%

Flow Cytometry and Effusions in Lymphoproliferative Processes and Other Hematologic Neoplasias

Bode-Lesniewska

2016

Acta Cytologica

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Cytopathologists are regularly confronted with lymphocyte-rich effusions, and the definite decision of whether the lymphocytosis is of a purely reactive nature or a presentation of an indolent lymphoma may be an extremely difficult one based on microscopy alone. Flow cytometry (FC) offers many advantages in terms of its application in body cavity fluids, and it has proven to be very useful both in the setting of a known disease and for new lymphoma diagnoses. In this paper, the studies published in recent years dealing with the applications of FC in body cavity effusions in the context of hematologic neoplasia are reviewed, stressing the integrative diagnostic approach. The incorporation of microscopical, immunophenotypical, and molecular findings from examinations of the cellular content of effusions and the interpretation of results in relation to the current WHO classification of hematolymphoid malignancies give cytopathologists new perspectives on advanced and clinically highly relevant diagnostics.

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Flow cytometry characterization in central nervous system and pleural effusion multiple myeloma infiltration: an Italian national cancer institute experience

Cited by 11 publications

References 10 publications

Aggressive and extramedullary plasma cell myeloma evade bone marrow flow cytometric minimal residual disease detection

Aggressive and extramedullary plasma cell myeloma evade bone marrow flow cytometric minimal residual disease detection

Brain stereotactic biopsy flow cytometry for central nervous system lymphoma characterization: advantages and pitfalls

Flow Cytometry and Effusions in Lymphoproliferative Processes and Other Hematologic Neoplasias

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