A case report of concurrent embryonal rhabdomyosarcoma and diffuse large B-cell lymphoma in an adult without identifiable cancer predisposition
- M. D. Mathias†1, 5Email author,
- M. V. Ortiz†1, 5,
- H. Magnan1, 5,
- S. R. Ambati1, 5,
- E. K. Slotkin1, 5,
- A. J. Chou1, 5,
- M. F. Walsh1, 5,
- K. Offit2, 5,
- C. Moskowitz3, 5,
- A. Kentsis1, 4, 5 and
- L. H. Wexler1, 5
© The Author(s). 2017
Received: 27 October 2016
Accepted: 3 February 2017
Published: 8 February 2017
Diffuse large B-cell lymphoma (DLBCL) is the most common form of non-Hodgkin lymphoma. Rhabdomyosarcoma, the most common soft tissue sarcoma of childhood. makes up less than 1% of solid malignancies in adults with around 400 new cases each year in the United States. They have not previously been reported concurrently.
A 37 year old woman presented with painful enlarging leg mass. Biopsy of the mass was consistent with embryonal rhabdomyosarcoma. Staging imaging revealed a PET avid anterior mediastinal lymph node. Excisional biopsy of this mass was consistent with diffuse large B-cell lymphoma. Hybridization capture-based next-generation DNA sequencing did not reveal shared somatic tumor mutations. Germline analysis did not show identifiable aberrations of TP53 or other heritable cancer susceptibility genes. She was treated with a personalized chemotherapy regimen combining features of R-CHOP and Children’s Oncology Group ARST 0331.
This case illustrates a unique clinical entity successfully treated with a personalized chemotherapeutic regimen.
KeywordsRhabdomyosarcoma Diffuse large B cell lymphoma Molecular analysis Case report
While usually sporadic in appearance, RMS has been seen in patients with cancer-predisposition syndromes such as Li-Fraumeni syndrome, neurofibromatosis type I, Costello syndrome, Noonan syndrome, and Beckwith-Wiedemann syndrome . There is also an increased risk of RMS in children with constitutional DICER1 mutations . Additionally, due to multimodal therapy with alkylating agents and radiation based therapy, these patients are also at risk of developing secondary malignancies. The last Childhood Cancer Survivor Study reported that 20% of patients with secondary malignancies were survivors of soft tissue sarcomas .
Diffuse large B-cell lymphoma (DLBCL) is the most common form of non-Hodgkin lymphoma. Heterogeneous in presentation and molecular pathology, it is characterized by aberrant proliferation of mature B-cells in nodal or extranodal sites . Therapy is based on extent of disease and presence or absence of ‘B symptoms’ and includes a multi-agent chemotherapy with targeted therapy including anti-CD20 antibodies. Genome wide association studies have shown independent single-nucleotide polymorphisms (SNPs) correlate with an increased risk of DLBCL [7, 8]. We report a woman with no significant prior medical history who was diagnosed with simultaneous ERMS and DLBCL. To our knowledge, the synchronous occurrence of these two tumors has not previously been reported in the medical literature. Next generation sequencing did not reveal a pervasive somatic or germline mutation that might link these tumors. Testing for a germline mutation consistent with a cancer predisposition syndrome failed to reveal identifiable abnormality of TP53 or any of the other genes associated with an increased risk of soft tissue sarcomas, in general, or rhabdomyosarcoma in particular.
Somatic tumor gene alterations within each tumor
Somatic Tumor Gene Alterations
Rhabdomyosarcoma of the Left Thigh
1. NF1 (NM_001042492) exon26 p.G1128fs (c.3382_3383delGG)
Diffuse Large B-Cell Lymphoma of the Anterior Mediastinum
1. ATM (NM_000051) exon58 p.S2860del (c.8578_8580delTCT)
2. B2M (NM_004048) exon1 p.L15fs (c.43_44delCT)
3. FAT1 (NM_005245) exon25 p.T4225M (c.12674C > T)
4. HGF (NM_000601) exon17 p.G660W (c.1978G > T)
5. MYCN (NM_005378) exon3 p.R393H (c.1178G > A)
6. PIM1 (NM_002648) exon4 p.L143M (c.427C > A)
7. SOCS1 (NM_003745) exon2 p.H87fs (c.258_268delGCACGGGGCGC)
8. SOCS1 (NM_003745) exon2 p.R92G (c.274C > G)
9. SOCS1 (NM_003745) exon2 p.S143N (c.428G > A)
10. SOCS1 (NM_003745) exon2 p.A184T (c.550G > A)
11. SOX317 (NM_022454) exon1 p.P49L (c.146C > T)
Individualized treatment regimen
Cyclophosphamide 1.2 gm/m2 IV x1
Dactinomycin 0.045 mg/kg IV x1
Doxorubicin 50 mg/kg IV x1
Prednisone 100 mg daily x5 days
Rituximab 375 m/m2 IV x1
Vincristine 1.5 mg/m2 IV x1
Disease surveillance scans
Discussion and Conclusions
We report an adult woman with no prior medical history nor familial cancer history who was diagnosed with synchronous RMS and DLBCL. Genomic analyses did not identify unifying somatic nor predisposing germline mutations. Although there is a prior report of a 64 year old man with concurrent RMS and Hodgkin lymphoma, to our knowledge this is the first case of RMS and any non-Hodgkin lymphoma .
Two distinct primary tumors without prior chemotherapy or radiation exposures or known underlying cancer predisposition is a rare entity that is poorly described. The simultaneous existence of two primary tumors presents a major therapeutic challenge, requiring the tailoring of a customized regimen that provides adequate therapy directed at each tumor without incurring intolerable toxicities. Cyclophosphamide, doxorubicin, vincristine, and prednisone are active against both RMS and DLBCL [11, 12]. It is likely that this overlapping chemotherapeutic sensitivity allowed the patient to tolerate the combined regimens of the COG RMS protocol with standard DLBCL therapy, R-CHOP.
The patient received a week pulse of steroids for pneumonia one month before she was diagnosed with RMS. This may have partially treated her DLBCL, causing her mediastinal mass to be less extensive than if untreated. A week-long steroid pre-phase is routinely utilized in the treatment of elderly patients with low performance status as a means of reducing initial treatment toxicities .
Despite genomic analyses, no unifying molecular aberration was identified in both of our patient’s two cancers. Archer et al. argued that the SEER-9 database provides population based evidence that subgroups of patients with rhabdomyosarcoma have constitutional cancer predisposition . At this point, further studies are required to delineate whether our patient had the unfortunate coincidence of two unrelated synchronous tumors or indeed represents part of a yet to be fully characterized cohort of patients with constitutional or inherited risk for rhabdomyosarcoma and other cancers.
Children’s oncology group
Diffuse large B-cell lymphoma
The authors would like to thank Dr. Narasimhan Agaram for providing the pathologic images shown in Figure 1.
This work was supported in part by the National Cancer Institute (NCI) Grant NIH T32 CA062948, the St. Baldricks Foundation Scholar who fund the salary of MM during the collection of data for this analysis and writing of the manuscript. All authors are partially funded by the MSK Cancer Center Support Grant/Core Grant P30 CA008748.
MM and MO had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. MM, MO, and LW were responsible for study concept and design. MM, MO, and LW drafted the manuscript. All authors helped to draft the manuscript. All authors read and approved the final manuscript.
The authors declare they have no competing interests.
Consent for publication
The patient and family gave consent to publish this form and signed our institutional form of consent.
Ethics approval and consent to participate
The patient and family gave assent and informed consent to all parts of this study and informed consent for publication.
Data deposition and access
Data Sharing not applicable to this article as no datasets were generated or analyzed during the study.
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