Homogeneously Staining Region (HSR) harboring CMYC amplification in a patient with primary plasma cell leukemia

Nusrat F Pathan, Margarita Palutke, Anwar N Mohamed  

Cytogenetic Laboratory, Pathology Department, Wayne State University School of Medicine, Detroit Medical Center, Detroit MI, USA

Previous history

Preleukaemia
-
Malignant disease
- no history of plasma cell myeloma or other malignancy
Inborn condition
-
Main items
+ Patient had solvent and formaldehyde exposures.

Clinics case report

Age
36 yrs
Sex
F
Liver
-
Spleen
-
Lymph nodes
-
Cns involv
-

Blood data

Wbc
14.4
Hb
11.1
Platelets
74
Bone marrow
Hypercellular marrow 100% with near-total replacement by sheets of malignant plasma cells ranging from small uninuclear to very large multinucleated cells with prominent nucleoli, and high mitotic activity (Figure 2A).
Note
WBC: 14.4x109/L 40% plasma cells with atypical features, Hb; 11.1g/dl, hematocrit of 33.5%, platelets; 74,000x109

Cyto path

Immunophenotype
Flow cytometry on peripheral blood showed an abnormal clonal plasma cell population expressing CD38, CD138, and dim CD45, with lambda chain restriction.
Rearranged ig tcr
Not performed.
Pathology
CT scan, MRI and bone scan revealed T5 soft tissue mass, multiple osteolytic lesions in skull, ribs, vertebra and iliac crest.
Electron microscopy
Not performed.
Precise diagnosis
Plasma cell leukemia (PCL).

Survival data

Date diagnosis
05-2008
Treatment
Steroid, Zometa, radiation, stem cell transplant.
Complete remission
- short remission.
Treatment relat death
-
Relapse
+ her disease recurred and spread to extramedullary sites spleen and lymph nodes; expired 5 months after diagnosis
Status
D
Date last follow
10-2008
Survival
5 from initial diagnosis

Karyotype

Sample
peripheral blood
Culture time
24 and 48 hours unstimulated cultures
Banding
GTG
Results
43,X,-X,del(1)(p13p36.1),-2,hsr(5)(q31),del(8)(q22q24.1),del(12)(q14q24.1),-13,t(14;16)(q32;q23),del(15)(q22),-16,del(17)(p11.2),hsr(17)(q24),add(20)(q13.3), +mar[cp14]/46,XX[6] (Figure 1).

Other molec studies

Technics
Fluorescence in situ hybridization using LSI D13S319/LAMP, TP53 and IGH/MAF DNA probes (Abbott Molecular) revealed loss of chromosome 13, deletion of p53 and IGH-MAF/t(14;16) in approximately 60% of interphase cells.
Results
Furthermore, hybridization with LSI IGH/CMYC/CEP-8 probe set showed that the two copies of hsr were entirely labeled with CMYC (Figure 2B).

Images

Atlas Image
Figure 1. G-banded karyotype showing two hsr regions (long arrows), t(14;16)(q32;q23) (short arrows) as well as other abnormalities.
Atlas Image
Figure 2. (A) Touch imprint of bone marrow biopsy showing several very large multinucleated as well as small uninuclear myeloma cells. (B) FISH analysis with LSI IGH/MYC/CEP8 tricolor, dual fusion translocation DNA probe set. The IGH is labeled with spectrum green, MYC with spectrum orange, and CEP 8 with spectrum aqua. (B) Hybridization of a metaphase showing 2 hsr regions (arrows), 3 IGH green signals, 1 orange MYC signal, and 2 aqua signals identifying chromosome 8. Notice one chromosome 8 has no MYC signal.

Comments section

Comments
The presence of an hsr in this case is also associated with a very bizarre plasma cell morphology and dismal clinical course. As seen in our patient, dmin and hsr have been described in association with deletion of 17p13/p53, suggesting that loss of p53 primes leukemic cells by increasing their survival, therefore allowing deregulation of other oncogenes such as CMYC and RAS. Still the molecular events that allow the plasma cells to escape the bone marrow environment are unclear. Sequential involvement and cooperation of multiple oncogenes and tumor suppressor genes, as well as other epigenetic events, are required for plasma cell expansion into the peripheral blood and extramedullary tissues.

Bibliography

Pubmed IDLast YearTitleAuthors
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99208531999Primary plasma cell leukemia: clinical, immunophenotypic, DNA ploidy, and cytogenetic characteristics.García-Sanz R et al
106184002000Diverse karyotypic abnormalities of the c-myc locus associated with c-myc dysregulation and tumor progression in multiple myeloma.Shou Y et al
111575062001Cytogenetic, interphase, and multicolor fluorescence in situ hybridization analyses in primary plasma cell leukemia: a study of 40 patients at diagnosis, on behalf of the Intergroupe Francophone du Myélome and the Groupe Français de Cytogénétique Hématologique.Avet-Loiseau H et al
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Citation

Nusrat F Pathan, Margarita Palutke, Anwar N Mohamed

Homogeneously Staining Region (HSR) harboring CMYC amplification in a patient with primary plasma cell leukemia

Atlas Genet Cytogenet Oncol Haematol. 2013-06-01

Online version: http://atlasgeneticsoncology.org/case-report/208866/homogeneously-staining-region-(hsr)-harboring-cmyc-amplification-in-a-patient-with-primary-plasma-cell-leukemia