- Email: [email protected]
Is it solitary plasmacytoma or nonsecretory myeloma? A must-be-solved dilemma?
Biomedicine & Pharmacotherapy 77 (2016) 27–29
Available online at
ScienceDirect www.sciencedirect.com
Short communication
Is it solitary plasmacytoma or nonsecretory myeloma? A must-be -solved dilemma? Kayhan Erturka,* , Didem Tastekina , Gokcen Gundogdub , Faruk Tasa , Sezai Vatansevera a b
Department of Medical Oncology, Institute of Oncology, Istanbul University Capa, 34093 Istanbul, Turkey Department of Pathology, Istanbul University, Capa, 34093 Istanbul, Turkey
A R T I C L E I N F O
A B S T R A C T
Article history: Received 9 August 2015 Accepted 23 November 2015
Presentation of multiple myeloma with bone lesions is common. It is vital that differentiation between nonsecretory multiple myeloma and plasmocytoma be done and that each disorder be treated accordingly. In this paper, we present a patient with nonsecretory multiple myeloma, who suffered from distal humerus fracture with severe bone destruction, renal failure, hypercalcemia and anemia. ã 2015 Elsevier Masson SAS. All rights reserved.
Keywords: Multiple myeloma Nonsecretory multiple myeloma Plasmocytoma Plasma cell dyscrasia
1. Introduction Multiple myeloma (MM) is characterized by clonal proliferation of plasma cells usually of the B cell type and accounts for approximately 10% of all hematologic malignancies [1] and 1–2% of all malignancies [1–3]. Bone pain, especially in the chest or back, is present in about 60% of patients with MM. Osteolytic bone lesions are the hallmark of the disease and patients generally suffer from pathologic fractures and vertebral collapse [1]. Diagnosis of MM requires 10% or more clonal plasma cells in the bone marrow and/ or pathological evidence of plasmocytoma and end-organ damage, such as hypercalcemia, renal insufficiency, anemia or bone lesions. Circulating monoclonal immunoglobulins (M protein) detected by serum or urine electrophoresis (SPEP and UPEP) and/or immunofixation (IF) are useful in making the diagnosis [4]. However, 1–5% of all symptomatic myelomas may present without detectable M proteins, thus they are termed nonsecretory multiple myeloma (NSMM) [5–7]. In these patients diagnosis is made either with bone marrow biopsy, which shows 10% or more clonal plasma cells [4] or by immunohistochemical analysis that further divides NSMM into two groups, nonsecretors and nonproducers [8]. The former subgroup stains cytoplasmic M-protein by immunohistochemically and constitutes 85% of the NSMM patients [9,10–12]. Since free light chains (FLC) assays (kappa/ lambda) (k/l) were recommended for making the diagnosis of NSMM, the percentage of nonproducers has even further decreased [8]. Defects in the synthesis and/or secretion and rapid
* Corresponding author. E-mail address: [email protected] (K. Erturk). http://dx.doi.org/10.1016/j.biopha.2015.11.004 0753-3322/ ã 2015 Elsevier Masson SAS. All rights reserved.
degradation of immunoglobulins are possible theories of the pathophysiology of NSMM [13]. As seen with MM, these patients may also present with end-organ damage attributable to the clonal plasma cell proliferation and their survival outcomes are comparable [14]. Differentiating NSMM from solitary plasmocytoma is usually challenging, in that they both might present with a single bone lesion and without detectable M-protein. These two different entities with different treatments, but similar manifestations might cause misdiagnosis of myeloma with solitary plasmocytoma, resulting in a delay of the systemic treatment [15]. In this paper, we present a patient with NSMM who suffered from distal humerus fracture with severe bone destruction, renal failure, hypercalcemia and anemia. 2. Case report A 65 year-old female was admitted to clinic with fractured right humerus. There was no history of fever, cough, headache, shortness of breath or any other fracture. Radiography showed a pathological fracture on the right distal humerus. The patient was anemic and had mild renal failure (Hb 9.5 g/dL and creatinine 1.6 mg/dL). Erythrocyte sedimentation rate (ESR), uric acid level, renal and liver function tests were within normal limits. Chest X-ray and abdominal ultrasound were normal. Computed tomography (CT) of the abdomen and chest showed a well-defined hypodense nodule in the isthmic location of thyroid and a lytic bone lesion and fracture on the right distal humerus. Positron emission tomography-computed tomography (PET/CT) scan demostrated increased fluorodeoxyglucose (FDG) uptake in the thyroid nodule and lytic
28
K. Erturk et al. / Biomedicine & Pharmacotherapy 77 (2016) 27–29
Fig. 1. Immunoreactivity with CD138 (HEx100).
Fig. 3. A typical plasma cells at high magnification (HEx400).
hypermetabolic lesions on the distal humerus. Thyroid cancer with bone metastasis was suspected and a fine needle biopsy of the thyroid revealed cytological findings with follicular neoplasia. The patient underwent bilateral total thyroidectomy. Pathological examination revealed a papillary carcinoma with follicular variant. One month later, the patients underwent radioactive iodine (RAI) therapy and one week later, she had a Iodine-131 whole body scintigraphy. The scintigraphy revealed bilateral radioiodine accumulations, with slightly more intense accumulation in the left lobe compared with the right lobe, and physiological radioiodine distribution in the remaining parts of the body. Meanwhile, due to severe bone destruction, the patient underwent a radical resection and prosthetic reconstruction surgery for distal humerus. Pathological examination of the excised humerus demonstrated a plasma cell neoplasia with k-light chain monotype. Upon this result, plasma cell disorder was suspected and additional tests were performed. Some of the laboratory data (the reference ranges are in brackets) of the patients were as follows: IgG 7.4 g/L (5.9– 15.6 g/L), IgA 1.4 g/L (0.6–5.0 g/L), and IgM 0.4 g/L (0.5–2.9 g/L). The low level of IgM was considered the consequence of humoral immunodepression that is often associated with multiple myeloma. FLC ratio was 2.96 (0.26–1.65). The pathological examination of the bone marrow aspirate and trephine biopsy showed a normocellular marrow with normal haemopoiesis replaced entirely with malignant plasma cells suggestive of myeloma (Figs. 1–4). Urine test was negative for Bence Jones protein and beta-2 microglobulin (b2 M) level was 8 mg/L (<2 mg/L). Mproteins were not detected on either serum or urine
electrophoresis and immunofixation. The calcium level was found as 14 mg/dL (8.4–10.6 mg/dL) and an immediate administration of isotonic saline (2 L over 1 h followed by 300 mL/h) was instituted. Once rehydration was complete, IV zoledronic acid was administered with a reduced dose (2 mg IV, infused over 30 min) because her creatinine cleareance was 52 mL/min at that time. The patients responded well and the calcium level dropped and remained within normal limits. Her urine output remained optimized during the course of her hospital stay. Because the diagnosis of NSMM, the patient received the combination chemotherapy regimen that consists of melphalan, prednisone and thalidomide, with a plan of 9 cycles induction therapy followed by maintenance with lenalidomide until progression or intolerance.
Diagnosis of solitary plasmocytoma requires all of the following criteria: biopsy proven solitary lesion of bone (osseous) or soft tissue (extraosseous) with evidence of clonal plasma cells, normal bone marrow with no evidence of clonal plasma cells, normal skeletal survey and magnetic resonance imaging (MRI) of spine and pelvis (except for the primary solitary lesion) and absence of end-organ damage such as hypercalcemia, renal insufficiency, anemia or bone lesions that can be attributed to a lympho-plasma cell proliferative disorder [4]. Diagnosis of asymptomatic MM (also referred to as smoldering MM), another variant of MM, must meet both of the following criteria; 3 g/dL or more serum M protein and/
Fig. 2. Immunoreactivity with Kappa (HEx100).
Fig. 4. A typical plasma cells with prominent nucleoli and mitosis at bone marrow (HEx200).
3. Discussion
K. Erturk et al. / Biomedicine & Pharmacotherapy 77 (2016) 27–29
or 10% or more clonal bone marrow plasma cells and absence of above mentioned end-organ damage [4]. The treatment protocols differ from one variant to the other. Asymptomatic MM requires no treatment therefore, it is monitored at 3–6 months intervals. On the other hand, primary treatments of solitary osseous and solitary extraosseous plasmocytomas are radiotherapy (45 Gy) to involved field and radiotherapy (45 Gy) to involved field and/or surgery, respectively. However, active (symptomatic) myeloma patients must be treated with systemic immunochemotherapy because in these patients radiotherapy plays only a palliative role [16]. Whenever any of the above mentioned varieties of MM is suspected, it is vital that the definitive diagnosis be made correctly and without delay. Misdiagnosis of symptomatic MM with plasmocytoma might lead to mis- and/or undertreatment. For the diagnosis of solitary plasmocytoma, a normal spinal and pelvic MRI (excluding the primary lesion) is imperative. The sensitivity of PET scan, MRI, CT and plain radiography are 86.3%, 83.3%, 70.4%, and 47.4%, respectively [3]. According to National Comprehensive Cancer Network (NCCN) Guidelines, these imaging techniques are optional for diagnosis of MM. In our patient, PET and CT scans were already performed, so the use of another imaging modality became unnecessary. Although MRI seems the most appropriate and more cost-effective imaging tool to diagnose NSMM/plasmocytoma and PET is not recommended in routine practice, PET scan, with the highest sensitivity among other imaging techniques, is useful when MRI results are negative or equivocal [15]. As recommended by working groups and guidelines, serum FLC analysis has become a part of making the diagnosis of myeloma and then in follow-up/surveillance of the disease [4,16,17]. In a number of published studies, serum FLC assays are indicated superiority over the urine tests in diagnosing of NSMM patients, particularly because these patients usually produce low levels of monoclonal free light chains (and, in fact, they are defined as hyposecretors rather than nonsecretors), but since the threshold of light chain production are not exceeded, free light chains are reabsorbed in the kidneys and measurable quantities are not overflown into the urine [8,18–20]. The patient, we described here, had high FLC ratio and this result concurs with the pathological examination of the excised humerus demostrated a plasma cell neoplasia with k-light chain monotype. The staging systems for MM consist of the Durie–Salmon Staging (DSS) criteria and the International Staging System (ISS) criteria [21,22]. Additionally, revised DSS criteria, DSS plus, have been developed. The latter includes MRI and/or PET scans results as well as original criteria. Durie–Salmon criteria evaluate mainly end-organ functions (Hb value, serum calcium value, renal function as subclassification criteria and the number of involved bones) and the rate of M protein production, whereas ISS focuses on serum b2 M and albumin levels. These classification systems divide the patients into 3 prognostic categories, stage 1, 2 and 3, with median overall survivals in moths, 62, 44 and 29, respectively. Our patient was DSS stage 3B and ISS stage 3. In conclusion, the clinicians can never be too overcautious when evaluating the patients with bone lesions. Once primary malignancy of and metastasis to the bone are excluded, then it is extremely important to differentiate plasmocytoma from NSSM. Every available diagnostic tool should be used as recommended to
29
avoid the delay of systemic immunochemotherapy due to misdiagnosis of symptomatic NSSM patients with plasmocytoma. Declaration of interest The authors report no declarations of interest. References [1] S.V. Rajkumar, A. Dispenzieri, Multiple Myeloma and Related Disorders, in: J.E. Niederhuber, J.O. Armitage, J.H. Doroshow, M.B. Kastan, J.E. Tepper (Eds.), Abeloff's Clinical Oncology, 5th ed., Elsevier Saunders, Philadelphia, PA, 2014, pp. 1991–1999. ska, Diagnosis and the current trends in multiple myeloma [2] A. Dmoszyn therapy, Pol. Arch. Med. Wewn. 118 (2008) 563–566. [3] A.P. Winterbottom, A.S. Shaw, Imaging patients with myeloma, Clin. Radiol. 64 (2009) 1–11. [4] A. Dispenzieri, R. Kyle, G. Merlini, J.S. Miguel, H. Ludwig, R. Hajek, A. Palumbo, S. Jagannath, J. Blade, S. Lonial, M. Dimopoulos, R. Comenzo, H. Einsele, B. Barlogie, K. Anderson, M. Gertz, J.L. Harousseau, M. Attal, P. Tosi, P. Sonneveld, M. Boccadoro, G. Morgan, P. Richardson, O. Sezer, M.V. Mateos, M. Cavo, D. Joshua, I. Turesson, W. Chen, K. Shimizu, R. Powles, S.W. Rajkumar, B.G. Durie, International Myeloma Working Group, International Myeloma Working Group guidelines for serum-free light chain analysis in multiple myeloma and related disorders, Leukemia 23 (2009) 215–224. [5] D.B. Smith, M. Harris, E. Gowland, J. Chang, J.H. Scarffe, Non-secretory multiple myeloma: report of 13 cases with review of literature, Haematol. Oncol. 4 (1986) 307–313. [6] I.A. Abdalla, I.A. Tabbara, Nonsecretory multiple myeloma, South Med. J. 95 (2002) 761–764. [7] R.A. Kyle, Ask the experts: nonsecretory myeloma, Myeloma Today 4 (2000) 2. [8] G.R. Shaw, Nonsecretory plasma cell myeloma becoming even more rare with serum free light-chain assay: a brief review, Arch. Pathol. Lab. Med. 130 (2006) 1212–1215. [9] J. Bladé, R. Kyle, Non-secretory multiple myeloma, immunoglobulin D myeloma, and plasma cell leukaemia, Haematol. Oncol. Clin. North Am. 13 (1999) 1259–1272. [10] M.S. Prakash, K.V. Baliga, A.P. Singh, D.K. Mishra, Non-secretory multiple myeloma with hypercalcemic acute renal failure, J. Assoc. Physicians India 50 (2002) 1330–1331. [11] J. Amir, W.B. Forman, A. Rassiga, G.M. Bernier, Nonsynthetizing multiple myeloma, Haematologia (Budap.) 11 (1977) 73–77. [12] T. Ishida, H.D. Dorfman, Plasma cell myeloma in unusually young patients: a report of two cases and review of the literature, Skeletal Radiol. 24 (1995) 47–51. [13] C. Decourt, H.R. Galea, C. Sirac, M. Cogne, Immunologic basis for the rare occurence of true nonsecretory plasma cell dyscrasias, J. Leukoc. Biol. 76 (2004) 528–536. [14] S. Kumar, W.S. Perez, M.J. Zhang, K. Ballen, A. Bashey, L.B. To, et al., Comparable outcomes in nonsecretory and secretory multiple myeloma after autologous stem cell transplantation, Biol. Blood Marrow Transplant. 14 (2008) 1134–1140. [15] L.P. Chen, T.H. Sun, P.P. Hsieh, L.J. Yen, S.J. Lin, M.S. Yu, Diagnostic pitfalls of nonsecretory myeloma manifesting as multiple foci of periosseous plasmacytomas, J. Chin. Med. Assoc. 74 (2011) 464–468. [16] National Comprehensive Cancer Network (NCCN) Guidelines Version 2. 2014, Multiple Myeloma. [17] G. Pratt, The evolving use of serum free light chain assay in haematology, Br. J. Haematol. 141 (2008) 413–422. [18] M. Drayson, L.X. Tang, R. Drew, G.P. Mead, H. Carr-Smith, A.R. Bradwell, Serum free light-chain measurements for identifying and monitoring patients with nonsecretory multiple myeloma, Blood 97 (2001) 2900–2902. [19] J.A. Katzmann, R.S. Abraham, A. Dispenzieri, J.A. Lust, R.A. Kyle, Diagnostic performance of quantitative kappa and lambda free light chain assays in clinical practice, Clin. Chem. 51 (2005) 878–881. [20] M.A. Alyanakian, A. Abbas, R. Delarue, B. Arnulf, P. Aucouturier, Free immunoglobulin light chain serum levels in the follow-up of patients with monoclonal gammopathies: correlation with 24-h urinary light-chain excretion, Am. J. Hematol. 75 (2004) 246–248. [21] B.G. Durie, S.E. Salmon, A clinical staging system for multiple myeloma, Cancer 36 (1975) 842–854. [22] P. Greipp, J. San Miguel, B. Durie, et al., International staging system for multiple myeloma, J. Clin. Oncol. 23 (2005) 3412–3420.
Available online at
ScienceDirect www.sciencedirect.com
Short communication
Is it solitary plasmacytoma or nonsecretory myeloma? A must-be -solved dilemma? Kayhan Erturka,* , Didem Tastekina , Gokcen Gundogdub , Faruk Tasa , Sezai Vatansevera a b
Department of Medical Oncology, Institute of Oncology, Istanbul University Capa, 34093 Istanbul, Turkey Department of Pathology, Istanbul University, Capa, 34093 Istanbul, Turkey
A R T I C L E I N F O
A B S T R A C T
Article history: Received 9 August 2015 Accepted 23 November 2015
Presentation of multiple myeloma with bone lesions is common. It is vital that differentiation between nonsecretory multiple myeloma and plasmocytoma be done and that each disorder be treated accordingly. In this paper, we present a patient with nonsecretory multiple myeloma, who suffered from distal humerus fracture with severe bone destruction, renal failure, hypercalcemia and anemia. ã 2015 Elsevier Masson SAS. All rights reserved.
Keywords: Multiple myeloma Nonsecretory multiple myeloma Plasmocytoma Plasma cell dyscrasia
1. Introduction Multiple myeloma (MM) is characterized by clonal proliferation of plasma cells usually of the B cell type and accounts for approximately 10% of all hematologic malignancies [1] and 1–2% of all malignancies [1–3]. Bone pain, especially in the chest or back, is present in about 60% of patients with MM. Osteolytic bone lesions are the hallmark of the disease and patients generally suffer from pathologic fractures and vertebral collapse [1]. Diagnosis of MM requires 10% or more clonal plasma cells in the bone marrow and/ or pathological evidence of plasmocytoma and end-organ damage, such as hypercalcemia, renal insufficiency, anemia or bone lesions. Circulating monoclonal immunoglobulins (M protein) detected by serum or urine electrophoresis (SPEP and UPEP) and/or immunofixation (IF) are useful in making the diagnosis [4]. However, 1–5% of all symptomatic myelomas may present without detectable M proteins, thus they are termed nonsecretory multiple myeloma (NSMM) [5–7]. In these patients diagnosis is made either with bone marrow biopsy, which shows 10% or more clonal plasma cells [4] or by immunohistochemical analysis that further divides NSMM into two groups, nonsecretors and nonproducers [8]. The former subgroup stains cytoplasmic M-protein by immunohistochemically and constitutes 85% of the NSMM patients [9,10–12]. Since free light chains (FLC) assays (kappa/ lambda) (k/l) were recommended for making the diagnosis of NSMM, the percentage of nonproducers has even further decreased [8]. Defects in the synthesis and/or secretion and rapid
* Corresponding author. E-mail address: [email protected] (K. Erturk). http://dx.doi.org/10.1016/j.biopha.2015.11.004 0753-3322/ ã 2015 Elsevier Masson SAS. All rights reserved.
degradation of immunoglobulins are possible theories of the pathophysiology of NSMM [13]. As seen with MM, these patients may also present with end-organ damage attributable to the clonal plasma cell proliferation and their survival outcomes are comparable [14]. Differentiating NSMM from solitary plasmocytoma is usually challenging, in that they both might present with a single bone lesion and without detectable M-protein. These two different entities with different treatments, but similar manifestations might cause misdiagnosis of myeloma with solitary plasmocytoma, resulting in a delay of the systemic treatment [15]. In this paper, we present a patient with NSMM who suffered from distal humerus fracture with severe bone destruction, renal failure, hypercalcemia and anemia. 2. Case report A 65 year-old female was admitted to clinic with fractured right humerus. There was no history of fever, cough, headache, shortness of breath or any other fracture. Radiography showed a pathological fracture on the right distal humerus. The patient was anemic and had mild renal failure (Hb 9.5 g/dL and creatinine 1.6 mg/dL). Erythrocyte sedimentation rate (ESR), uric acid level, renal and liver function tests were within normal limits. Chest X-ray and abdominal ultrasound were normal. Computed tomography (CT) of the abdomen and chest showed a well-defined hypodense nodule in the isthmic location of thyroid and a lytic bone lesion and fracture on the right distal humerus. Positron emission tomography-computed tomography (PET/CT) scan demostrated increased fluorodeoxyglucose (FDG) uptake in the thyroid nodule and lytic
28
K. Erturk et al. / Biomedicine & Pharmacotherapy 77 (2016) 27–29
Fig. 1. Immunoreactivity with CD138 (HEx100).
Fig. 3. A typical plasma cells at high magnification (HEx400).
hypermetabolic lesions on the distal humerus. Thyroid cancer with bone metastasis was suspected and a fine needle biopsy of the thyroid revealed cytological findings with follicular neoplasia. The patient underwent bilateral total thyroidectomy. Pathological examination revealed a papillary carcinoma with follicular variant. One month later, the patients underwent radioactive iodine (RAI) therapy and one week later, she had a Iodine-131 whole body scintigraphy. The scintigraphy revealed bilateral radioiodine accumulations, with slightly more intense accumulation in the left lobe compared with the right lobe, and physiological radioiodine distribution in the remaining parts of the body. Meanwhile, due to severe bone destruction, the patient underwent a radical resection and prosthetic reconstruction surgery for distal humerus. Pathological examination of the excised humerus demonstrated a plasma cell neoplasia with k-light chain monotype. Upon this result, plasma cell disorder was suspected and additional tests were performed. Some of the laboratory data (the reference ranges are in brackets) of the patients were as follows: IgG 7.4 g/L (5.9– 15.6 g/L), IgA 1.4 g/L (0.6–5.0 g/L), and IgM 0.4 g/L (0.5–2.9 g/L). The low level of IgM was considered the consequence of humoral immunodepression that is often associated with multiple myeloma. FLC ratio was 2.96 (0.26–1.65). The pathological examination of the bone marrow aspirate and trephine biopsy showed a normocellular marrow with normal haemopoiesis replaced entirely with malignant plasma cells suggestive of myeloma (Figs. 1–4). Urine test was negative for Bence Jones protein and beta-2 microglobulin (b2 M) level was 8 mg/L (<2 mg/L). Mproteins were not detected on either serum or urine
electrophoresis and immunofixation. The calcium level was found as 14 mg/dL (8.4–10.6 mg/dL) and an immediate administration of isotonic saline (2 L over 1 h followed by 300 mL/h) was instituted. Once rehydration was complete, IV zoledronic acid was administered with a reduced dose (2 mg IV, infused over 30 min) because her creatinine cleareance was 52 mL/min at that time. The patients responded well and the calcium level dropped and remained within normal limits. Her urine output remained optimized during the course of her hospital stay. Because the diagnosis of NSMM, the patient received the combination chemotherapy regimen that consists of melphalan, prednisone and thalidomide, with a plan of 9 cycles induction therapy followed by maintenance with lenalidomide until progression or intolerance.
Diagnosis of solitary plasmocytoma requires all of the following criteria: biopsy proven solitary lesion of bone (osseous) or soft tissue (extraosseous) with evidence of clonal plasma cells, normal bone marrow with no evidence of clonal plasma cells, normal skeletal survey and magnetic resonance imaging (MRI) of spine and pelvis (except for the primary solitary lesion) and absence of end-organ damage such as hypercalcemia, renal insufficiency, anemia or bone lesions that can be attributed to a lympho-plasma cell proliferative disorder [4]. Diagnosis of asymptomatic MM (also referred to as smoldering MM), another variant of MM, must meet both of the following criteria; 3 g/dL or more serum M protein and/
Fig. 2. Immunoreactivity with Kappa (HEx100).
Fig. 4. A typical plasma cells with prominent nucleoli and mitosis at bone marrow (HEx200).
3. Discussion
K. Erturk et al. / Biomedicine & Pharmacotherapy 77 (2016) 27–29
or 10% or more clonal bone marrow plasma cells and absence of above mentioned end-organ damage [4]. The treatment protocols differ from one variant to the other. Asymptomatic MM requires no treatment therefore, it is monitored at 3–6 months intervals. On the other hand, primary treatments of solitary osseous and solitary extraosseous plasmocytomas are radiotherapy (45 Gy) to involved field and radiotherapy (45 Gy) to involved field and/or surgery, respectively. However, active (symptomatic) myeloma patients must be treated with systemic immunochemotherapy because in these patients radiotherapy plays only a palliative role [16]. Whenever any of the above mentioned varieties of MM is suspected, it is vital that the definitive diagnosis be made correctly and without delay. Misdiagnosis of symptomatic MM with plasmocytoma might lead to mis- and/or undertreatment. For the diagnosis of solitary plasmocytoma, a normal spinal and pelvic MRI (excluding the primary lesion) is imperative. The sensitivity of PET scan, MRI, CT and plain radiography are 86.3%, 83.3%, 70.4%, and 47.4%, respectively [3]. According to National Comprehensive Cancer Network (NCCN) Guidelines, these imaging techniques are optional for diagnosis of MM. In our patient, PET and CT scans were already performed, so the use of another imaging modality became unnecessary. Although MRI seems the most appropriate and more cost-effective imaging tool to diagnose NSMM/plasmocytoma and PET is not recommended in routine practice, PET scan, with the highest sensitivity among other imaging techniques, is useful when MRI results are negative or equivocal [15]. As recommended by working groups and guidelines, serum FLC analysis has become a part of making the diagnosis of myeloma and then in follow-up/surveillance of the disease [4,16,17]. In a number of published studies, serum FLC assays are indicated superiority over the urine tests in diagnosing of NSMM patients, particularly because these patients usually produce low levels of monoclonal free light chains (and, in fact, they are defined as hyposecretors rather than nonsecretors), but since the threshold of light chain production are not exceeded, free light chains are reabsorbed in the kidneys and measurable quantities are not overflown into the urine [8,18–20]. The patient, we described here, had high FLC ratio and this result concurs with the pathological examination of the excised humerus demostrated a plasma cell neoplasia with k-light chain monotype. The staging systems for MM consist of the Durie–Salmon Staging (DSS) criteria and the International Staging System (ISS) criteria [21,22]. Additionally, revised DSS criteria, DSS plus, have been developed. The latter includes MRI and/or PET scans results as well as original criteria. Durie–Salmon criteria evaluate mainly end-organ functions (Hb value, serum calcium value, renal function as subclassification criteria and the number of involved bones) and the rate of M protein production, whereas ISS focuses on serum b2 M and albumin levels. These classification systems divide the patients into 3 prognostic categories, stage 1, 2 and 3, with median overall survivals in moths, 62, 44 and 29, respectively. Our patient was DSS stage 3B and ISS stage 3. In conclusion, the clinicians can never be too overcautious when evaluating the patients with bone lesions. Once primary malignancy of and metastasis to the bone are excluded, then it is extremely important to differentiate plasmocytoma from NSSM. Every available diagnostic tool should be used as recommended to
29
avoid the delay of systemic immunochemotherapy due to misdiagnosis of symptomatic NSSM patients with plasmocytoma. Declaration of interest The authors report no declarations of interest. References [1] S.V. Rajkumar, A. Dispenzieri, Multiple Myeloma and Related Disorders, in: J.E. Niederhuber, J.O. Armitage, J.H. Doroshow, M.B. Kastan, J.E. Tepper (Eds.), Abeloff's Clinical Oncology, 5th ed., Elsevier Saunders, Philadelphia, PA, 2014, pp. 1991–1999. ska, Diagnosis and the current trends in multiple myeloma [2] A. Dmoszyn therapy, Pol. Arch. Med. Wewn. 118 (2008) 563–566. [3] A.P. Winterbottom, A.S. Shaw, Imaging patients with myeloma, Clin. Radiol. 64 (2009) 1–11. [4] A. Dispenzieri, R. Kyle, G. Merlini, J.S. Miguel, H. Ludwig, R. Hajek, A. Palumbo, S. Jagannath, J. Blade, S. Lonial, M. Dimopoulos, R. Comenzo, H. Einsele, B. Barlogie, K. Anderson, M. Gertz, J.L. Harousseau, M. Attal, P. Tosi, P. Sonneveld, M. Boccadoro, G. Morgan, P. Richardson, O. Sezer, M.V. Mateos, M. Cavo, D. Joshua, I. Turesson, W. Chen, K. Shimizu, R. Powles, S.W. Rajkumar, B.G. Durie, International Myeloma Working Group, International Myeloma Working Group guidelines for serum-free light chain analysis in multiple myeloma and related disorders, Leukemia 23 (2009) 215–224. [5] D.B. Smith, M. Harris, E. Gowland, J. Chang, J.H. Scarffe, Non-secretory multiple myeloma: report of 13 cases with review of literature, Haematol. Oncol. 4 (1986) 307–313. [6] I.A. Abdalla, I.A. Tabbara, Nonsecretory multiple myeloma, South Med. J. 95 (2002) 761–764. [7] R.A. Kyle, Ask the experts: nonsecretory myeloma, Myeloma Today 4 (2000) 2. [8] G.R. Shaw, Nonsecretory plasma cell myeloma becoming even more rare with serum free light-chain assay: a brief review, Arch. Pathol. Lab. Med. 130 (2006) 1212–1215. [9] J. Bladé, R. Kyle, Non-secretory multiple myeloma, immunoglobulin D myeloma, and plasma cell leukaemia, Haematol. Oncol. Clin. North Am. 13 (1999) 1259–1272. [10] M.S. Prakash, K.V. Baliga, A.P. Singh, D.K. Mishra, Non-secretory multiple myeloma with hypercalcemic acute renal failure, J. Assoc. Physicians India 50 (2002) 1330–1331. [11] J. Amir, W.B. Forman, A. Rassiga, G.M. Bernier, Nonsynthetizing multiple myeloma, Haematologia (Budap.) 11 (1977) 73–77. [12] T. Ishida, H.D. Dorfman, Plasma cell myeloma in unusually young patients: a report of two cases and review of the literature, Skeletal Radiol. 24 (1995) 47–51. [13] C. Decourt, H.R. Galea, C. Sirac, M. Cogne, Immunologic basis for the rare occurence of true nonsecretory plasma cell dyscrasias, J. Leukoc. Biol. 76 (2004) 528–536. [14] S. Kumar, W.S. Perez, M.J. Zhang, K. Ballen, A. Bashey, L.B. To, et al., Comparable outcomes in nonsecretory and secretory multiple myeloma after autologous stem cell transplantation, Biol. Blood Marrow Transplant. 14 (2008) 1134–1140. [15] L.P. Chen, T.H. Sun, P.P. Hsieh, L.J. Yen, S.J. Lin, M.S. Yu, Diagnostic pitfalls of nonsecretory myeloma manifesting as multiple foci of periosseous plasmacytomas, J. Chin. Med. Assoc. 74 (2011) 464–468. [16] National Comprehensive Cancer Network (NCCN) Guidelines Version 2. 2014, Multiple Myeloma. [17] G. Pratt, The evolving use of serum free light chain assay in haematology, Br. J. Haematol. 141 (2008) 413–422. [18] M. Drayson, L.X. Tang, R. Drew, G.P. Mead, H. Carr-Smith, A.R. Bradwell, Serum free light-chain measurements for identifying and monitoring patients with nonsecretory multiple myeloma, Blood 97 (2001) 2900–2902. [19] J.A. Katzmann, R.S. Abraham, A. Dispenzieri, J.A. Lust, R.A. Kyle, Diagnostic performance of quantitative kappa and lambda free light chain assays in clinical practice, Clin. Chem. 51 (2005) 878–881. [20] M.A. Alyanakian, A. Abbas, R. Delarue, B. Arnulf, P. Aucouturier, Free immunoglobulin light chain serum levels in the follow-up of patients with monoclonal gammopathies: correlation with 24-h urinary light-chain excretion, Am. J. Hematol. 75 (2004) 246–248. [21] B.G. Durie, S.E. Salmon, A clinical staging system for multiple myeloma, Cancer 36 (1975) 842–854. [22] P. Greipp, J. San Miguel, B. Durie, et al., International staging system for multiple myeloma, J. Clin. Oncol. 23 (2005) 3412–3420.