Treating a Simultaneous Presentation of Multiple Myeloma and Hodgkin’s Lymphoma

    

    

    Figure 2:  Right femur bone biopsy (left) was almost entirely occupied
by sheets of plasma cells, supported with CD138. Staining notable for
monoclonal populations of kappa and IgG. Immunohistochemistry stains from
the retroperitoneal lymph node biopsy (right) were CD30, CD15, and PAX5
positive.
    
    

Positron emission tomography–computed tomography (PETCT) demonstrated, in addition to lytic lesions, hypermetabolic adenopathy in the abdomen and mediastinum. Two right inguinal lymph node biopsies were performed with pathology showing benign fat infiltration. With a high suspicion for pathologic lymphadenopathy, a repeat biopsy of a retroperitoneal lymph node was performed and demonstrated classical nodular sclerosing HL. Immunohistochemistry stains showed neoplastic cells that were CD30, CD15, and PAX5 positive (Figure 2). They were CD45, CD3, and CD20 negative. Ebstein-Barr virus latent membrane protein was also negative. Staging of HL was difficult considering an overlapping diagnosis of symptomatic MM but was considered stage III with lymphatic involvement above and below the diaphragm by the Ann Arbor staging system.

Initial treatment was determined at a multidisciplinary tumor board. For treatment of HL, the patient was started on doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) therapy and underwent six cycles. Bleomycin was not given in cycle numbersix due to lung toxicity. Treatment for consisted of 20 mg of dexamethasone weekly and 4 mg zoledronic acid injections every 4 weeks while she received ABVD chemotherapy. She subsequently demonstrated regression of her lymphadenopathy with a Deauville criteria of one on the final PET-CT, but the bone lesions remained hypermetabolic. Biopsy of the sacral bone lesion confirmed active MM. Electrophoresis showed reduction in the IgG Kappa M protein spike (from 0.5 to 0.1 mg/dL) and reduction of the kappa/lambda free light chain ratio after treatment of HL with ABVD and weekly dexamethasone. Treatment for MM was initiated after completion of ABVD, with weekly bortezomib subcutaneous injections and oral dexamethasone for a total of 16 cycles. She was evaluated for autologous bone marrow transplant but deemed not to be a suitable candidate due to her comorbidities. The patient has been followed without progression of disease for over two years.

Discussion

MM does not present with lymphadenopathy, which prompted further investigation in our patient. In this case, the patient was found to have a second malignancy. If the diagnosis of HL was not made it may have resulted in significant morbidity and mortality for the patient from an otherwise curable disease. Therapeutic management was complicated by two different malignancies with different treatment regimens. Based on previous case reports and interdisciplinary meetings, it was decided to first focus treatment on the curable disease, HL, and concurrently provides partial treatment for MM. After radiation therapy for the MM bone lesions, treatment with ABVD was initiated for HL and well as oral dexamethasone and zometa injections for MM. The diagnosis of HL prior to initiating therapy for MM was significant in that different regimens reserved for more aggressive treatment of MM would have been used had the second diagnosis not been made, such as bortezomib, lenalidomide, and dexamethasone.

There are a handful of published case reports of concurrent presentations of MM and HL prior to initiating treatment [1-6]. Some of these cases describe similar treatment regimens involving initial use of ABVD therapy. One case describes the diagnosis of HL after bortezomib and dexamethasone were initiated for the treatment of MM [7]. Bortezomib and dexamethasone were stopped with the diagnosis of HL, and ABVD therapy initiated. Another case describes delayed diagnosis of HL after MM was diagnosed and treatment had to be altered [8]. An international study used the addition ofthalidomide to the standard AVBD regimen [3]. In this study, the patient declined transplantation and was given continued cycles of dexamethasone and thalidomide to avoid disease progression. All studies treated with chemotherapy until complete remission of HL was achieved and then preceded to ASCT if possible. We present a regimen in which AVBD therapy, dexamethasone, and zoledronic acid injections are provided concurrently followed by bortezomib and dexamethasone.

Considering that MM is derived from B cells that mature into plasma cells and that HL is derived from germinal B cells, it is rational to theorize that similar risk factors causing one malignancy may then trigger evolution of the other malignancy [9-12]. In fact, one recent study describes the identification of genetic risk factors related to the development of B cell malignancies [13]. These risk factors involved specific loci that were found to cause pleotropic effects on the regulation of the B cell pathway, resulting in either increased or decreased risk of developing MM, HL, and chronic lymphocytic leukemia. This pathway not only describes how multiple B cell pathway related malignancies may occur subsequently or concurrently but also suggests possible therapeutic targets for these malignancies in the future.

Our case illustrates two main concepts: the importance of investigating the etiology of pathologic lymphadenopathy despite an initial negative biopsy, and a successful treatment regimen used in a patient diagnosed with simultaneous HL and MM.