CA-125 secreting IgG kappa multiple myeloma
Authors: mariam boota, carolina schinke, shawn ledoux, daisy alapat, rashid khan, bart barlogie
Journal: American Journal of Hematology (2016)

To the Editor: Multiple myeloma (MM) is a malignant plasma cell disorder that comprises 10% of all hematological malignancies. Despite recent advances in therapy, MM is widely recognized as incurable disease with 5 year overall survival of around 50% (SEER) 1. Clinical diagnosis is based on manifestation of end organ damage including hypercalcemia, renal failure, anemia, and bone lesions. Although tumor markers have an established clinical significance, there are no clinically validated bio-markers in myeloma practice currently. We are presenting an interesting case of a CA-125 secreting myeloma, where CA-125 correlated with overall tumor burden and was also used to assess response to therapy along with conventional myeloma disease markers. CA-125, is a mucin-like glycoprotein with a 200,000 Da molecular weight expressed in coelomic epithelium during embryonic development. Its role has been described in several malignant, non-malignant, and certain physiological states and is usually secreted by the mesothelial cells 2. CA-125 elevation in the setting of MM is rare and to our best knowledge this is the first case to show CA-125 being produced by the patient's CD-138 +ve plasma cells. Although a prior case has been reported but the source was not validated 3. The patient is a 55-year-old female with history of localized cervical cancer, who presented to the Myeloma Institute with a diagnosis of IgG kappa Durie Salmon stage II-A MM in April 2003. She was diagnosed previously with cervical cancer in 1997, treated with curative intent with hysterectomy without adjuvant radiation or chemotherapy. She was then followed up annually until March of 2002, when she manifested an asymptomatic elevation of CA-125 level to 500 U/mL. The findings lead to multiple radiographic imaging followed by surgical exploration which was negative for malignancy. However, in November 2002 patient experienced back pain and skeletal survey and CT-scan of the abdomen revealed a 3-inch tumor lesion in the pelvis which was subjected to a CT-guided biopsy revealing plasmacytoma on pathology. Further work up revealed bone marrow plasmacytosis of 20%, IgG 2470 mg/dL, serum M-protein 2.4 g/dL, beta-2-microglobulin 2.5 mg/L, and hemoglobin of 11.2 g/dL. Serum and urine immunofixation was positive for IgG kappa free light chains. The patient was started on induction with VAD (Vincristine, Doxorubicin, and Dexamethasone) for four cycles between December 2002 and March 2003, which led to a partial response demonstrated by a 50% reduction in serum M-protein and IgG levels. She was then referred to our center for further work up which revealed bone marrow plasmacytosis of 10–20%, serum M protein 1.8, IgG level 2,930 mg/dL, serum free kappa light chains of 31.3 mg/dL, beta-2-microglobulin 2.1, and hemoglobin of 11.5 g/dL. Urine immunofixation showed IgG kappa plus free kappa light chain Bence-Jones proteinuria. CA-125 level was 196 U/mL. Baseline PET-CT did not reveal any bony focal lesions, or evidence of extra-medullary disease. Hence a diagnosis of IgG kappa multiple myeloma was made and she was enrolled on a clinical research protocol (UARK 2001-12) under which she received a single unfractionated Melphalan 200 mg/m2 stem cell transplant post DTPACE (Dexamethasone, Thalidomide, Cisplatin, Doxorubicin, Cyclophosphamide, and Etoposide) induction in June 2003. Interestingly, repeat CA-125 level in August 2003 showed a drastic decline to 81 U/mL from 500 U/mL after her treatment, which prompted the hypothesis that CA-125 was secreted by plasma cells. Histopathologic evaluation confirmed that the patient's CD-138 +ve plasma cells were the source of CA-125 production. CA-125 staining of bone marrow showed a characteristic faint membranous pattern within neoplastic plasma cells which is shown in Fig. 1 The patient has been followed up to date and has been on and off several anti-myeloma therapies with her CA-125 levels following overall disease bulk. A: Rare plasma cells are identified on the hematoxylin and eosin stained sections of bone marrow. B: CA-125 stained sections of bone marrow highlights a faint membranous staining pattern within neoplastic plasma cells. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.] CA 125 is an important tumor marker for diagnosis and follow-up of ovarian epithelial carcinomas 4. However like most bio-markers in clinical use, it is non-specific and has been reported in other malignant conditions, such as acute leukemia associated with extra medullary localization and serosal effusion, Hodgkin's and non-Hodgkin's lymphoma, and solid tumors such as lung, breast, GI-malignancies, and melanoma 5. MM with CA-125 elevation is thought to be rare, however CA-125 testing is not routinely performed and elevated CA-125 might be missed easily. Our case shows that CA-125 can be elevated in MM and is secreted by Plasma cells. Further evaluation of CA-125 elevation in MM and its possible role as tumor marker is warranted. Mariam Boota,1* Carolina Schinke,1 Shawn Ledoux,2 Daisy Alapat,2 Rashid Khan,1 and Bart Barlogie1 1Myeloma Institute, University of Arkansas for Medical Sciences, Little Rock, Arkansas 2Pathology Department, University of Arkansas for Medical Sciences, Little Rock, Arkansas