RESUMO
This study analyzed 140 patients with isolated del13q14 on interphase FISH (I-FISH), to identify subsets with a different progression risk and to assess the acquisition of additional chromosomal abnormalities (clonal evolution) in treatment-naïve del13q14 patients. A monoallelic deletion (del13qx1) was detected in 123 cases (88%), a biallelic deletion (del13qx2) in eight and a mosaic of monoallelic and biallelic deletions (del13qx1/del13qx2) in nine. In 33% of cases, deletion encompassed the Rb1 locus The median percentage of abnormal nuclei was 50% (15%-96%), and it was higher in patients with a biallelic/mosaic pattern in comparison with patients with monoallelic deletion. Sixty two patients (44%) have been treated; 5-year treatment free survival rate was 56% and the median treatment free survival was 65 months. The baseline percentage of deleted nuclei, as a continuous variable, was related to progression (HR: 1.02; p = 0.001). According to deletion burden, three groups were identified: 64 cases (46%) had <50% deleted nuclei, 47 (33%) had 50-69% deleted nuclei, and 29 (21%) had ≥70% deleted nuclei. The 5-year untreated rate was 70.5% , 52.6% and 28.7% (p < 0.0001), respectively. In multivariate analysis using IGHV mutational status, presence of a nullisomic clone, CD38 expression and percentage of deleted nuclei as covariates, only IGHV mutational status and the percentage of deleted nuclei were independent risk factors for treatment. In 103 patients serially monitored by I-FISH before starting any treatment, we observed a significant increase in the proportion of del13q14 cells, and this increase affected the risk of subsequent treatment requirement (HR 2.54, p = 0.001). The appearance of a new clone was detected in 16 patients (15.5%) and chromosome 13 was involved in 14 of them. I-FISH monitoring proves worthwhile for a dynamic risk stratification and for planning clinical surveillance.
Assuntos
Deleção Cromossômica , Cromossomos Humanos Par 13/genética , Hibridização in Situ Fluorescente/métodos , Leucemia Linfocítica Crônica de Células B/genética , ADP-Ribosil Ciclase 1/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Núcleo Celular/ultraestrutura , Células Clonais/ultraestrutura , Progressão da Doença , Intervalo Livre de Doença , Feminino , Seguimentos , Deleção de Genes , Genes do Retinoblastoma , Humanos , Interfase/genética , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Masculino , Glicoproteínas de Membrana/genética , Pessoa de Meia-Idade , Proteínas de Neoplasias/genética , Prognóstico , Modelos de Riscos Proporcionais , Proteína do Retinoblastoma/deficiência , Proteína do Retinoblastoma/genética , Risco , Proteína-Tirosina Quinase ZAP-70/genéticaRESUMO
A 40-year-old male presented with abdominal distension and dyspnea. On evaluation found to have hepatic plasmacytoma without marrow clonal plasma cells. Fluorescent in situ hybridization (FISH) on tissue biopsy revealed myeloma-defining cytogenetics. After treating with novel agents, the patient had a complete response to therapy.
RESUMO
Plasmablastic myeloma (PBM) is a blastic morphologic variant of plasma cell myeloma with less favorable prognosis than those with non-blastic morphology. PBM is rare, without clear-cut definition and detailed clinicopathologic features in the literature. PBM may mimic plasmablastic lymphoma (PBL) as they share nearly identical morphology and immunophenotype. Using the criteria of ≥ 30% plasmablasts in tissue sections, we retrospectively recruited PBM cases and analyzed their clinical, imaging, and pathologic findings, with emphasis on extramedullary involvement. We performed immunohistochemistry, in situ hybridization for Epstein-Barr virus (EBER), and fluorescence in situ hybridization (FISH) for lymphoma- and myeloma-associated genetic alterations. Of the 25 recruited cases, 15 (60%) had extramedullary involvement, which occurred as initial presentation in nine cases. The most common extramedullary sites were soft tissue and/or skin (10/15, 67%), followed by pleural effusion, the lungs, and lymph nodes. Immunohistochemically, tumor cells expressed MYC (74%; 17/23), CD56 (56%; 14/25), and cyclin D1 (16%; 4/25), while CD117 was all negative (n = 25). Of the 20 cases stained with p53, four (20%) cases were diffusely positive, and the remaining 16 cases showed a heterogeneous pattern. EBER was negative in all 24 cases examined. Of the 13 cases examined with FISH, the genetic aberrations identified included del(13q14)(92%; 12/13), gain of chromosome 1q (90%; 9/10), loss of chromosome 1p (60%; 6/10), IGH-FGFR3 reciprocal translocation (23%; 3/13), rearranged MYC (15%; 2/13), and rearranged CCND1 (8%; 1/13), while there were no cases with TP53 deletion (n = 10) or rearrangement of BCL2 (n = 13) or BCL6 (n = 13). The prognosis was dismal regardless of the presence or absence of extramedullary involvement. In conclusion, PBM in Taiwan frequently presented as extramedullary and extranodal lesions, particularly in soft tissue and/or skin, mimicking PBL. FISH for targeted genetic alterations such as del(13q14), gain of chromosome 1q, loss of chromosome 1p, and IGH-FGFR3 might be helpful for the differential diagnoses. Larger studies are warranted to investigate the genetic alterations between PBM and PBL.