MGUS with t(11;14) and t(14;16) in Different Cell Clones
Authors: Hinrichsen Tanja , Klein Hanns-Georg , Schmidt Burkhard 
Published: October 2019

Abstract
A 75-year-old patient with slowly increasing polyneuropathy (PNP) (sensitive PNP, WHO°2), pre-existing for 6 months, in conjunction with a monoclonal gammopathy (IgG/kappa) is presented. Significant pre-existing conditions (for example, diabetes) do not exist. The physical examination findings and abdominal sonography are unremarkable. Serum values: M-gradient in the gamma fraction of the electrophoresis. IgG 11.58 g/L (standard 7.0 - 16.0) with decreased values for IgA 0.29 (standard 0.7-4.0) and IgM 0.21 (standard 0.4 to 2.3). Free light chains: kappa 152 mg/L (6.7 - 22.4), lambda 6.5 mg/l (8.3 - 27), kappa/lambda ratio: 23.49 (0.31 - 1.56). A bone marrow puncture showed 8% clonal plasma cells as well as an unremarkable set of female chromosomes.
The FISH analysis of CD138+ enriched cells showed the following changes:
- Vysis LSI ATM/CEP 11: 3 r + 2 gr (40/209)
- MetaSystems XL DLEU/TP53: 1 r + 2 gr (31/231)
- MetaSystems XL IGH plus: 1 F (r/gr) + 1 r + 1 gr (35/229) and 2 r + 1 gr (39/229)
- MetaSystems XL t(11;14): 2 r + 3 gr (27/224) and 3 F (r/gr) + 1 r (88/224)
- MetaSystems XL t(14;16): 2 r + 3 gr (57/232) and 2 F (r/gr) + 1 r + 1 gr (51/232)
Consequently, FISH analysis found a deletion in the region 13q14 (DLEU) in 13.4% of the interphases, a balanced translocation t(14;16)(q32;q23) in 22.0% of the interphases and a balanced translocation t(11;14)(q13;q32) in 39.3% of the interphases, as well as an altered chromosome 14 from an unbalanced translocation t(11;14)(q13;q32). The unbalanced translocation results in a loss of chromosome material from 14q32->14qter and a gain in chromosome material from 11q13->11qter (confirmed by gain of ATM (11q22.3)). In addition, it was shown that the 13q14 deletion is associated with the translocation t(14;16)(q32;q23) and that the translocation t(11;14)(q13;q32) represents an independent cell clone.
Computed tomography of the skeletal system showed isolated small osteolyses in the skullcap (the differential diagnosis could also be the physiologically occurring Pacchionian granulations), and osteoporosis of the spine. Clear CRAB criteria (hypercalcemia, renal failure, anemia, myeloma typical osteolytic lesions) are not available. Since PNP constitutes a treatment indication outside the CRAB criteria, it was recommended the patient start treatment to slow the progression of PNP. In principle, bortezomib belongs to the standard repertoire of first-line treatment in patients ineligible for high-dose therapy and stem cell transplantation (among other factors age >75 years). It is however problematic that an adverse effect of bortezomib is to induce PNP. Thalidomide, another effective preparation of the first-line treatment of elderly patients, is also rarely used due to this. In the last few months, the patient was recommended therapy with an approved combination of lenalidomide and dexamethasone as first-line therapy, and treatment has now started.

Disclosures
Hinrichsen: Center for Human Genetics and Laboratory Diagnostics (AHC) Dr. Klein, Dr. Rost and Colleagues: Employment. Klein:Zentrum für Humangenetik und Laboratoriumsdiagnostik Dr. Klein, Dr. Rost und Kollegen: Equity Ownership.