Case Report
A case of multiple myeloma with navicular bone involvement
Scottish Medical Journal 0(0) 1–4 ! The Author(s) 2017 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/0036933017727962 journals.sagepub.com/home/scm
Esra Yildizhan1, Leylagul Kaynar2, Nicolette Tiren1, Ozlem canoz3 and Bulent Eser4
Abstract Multiple myeloma is a haematological disease caused by proliferation of malignant plasma cells in bone marrow. It frequently has lytic bone lesions. However, involvement of the small bones of the hands and feet is extremely rare. We report a unique multiple myeloma patient with first recurrence in navicular bone after allogenic stem cell transplantation.
Keywords Multiple myeloma, navicular bone
Introduction Multiple myeloma (MM) is a neoplastic disorder characterised by malignant proliferation of clonal plasma cells in bone marrow, aberrant production of monoclonal immunoglobulins (paraprotein), and end organ damage, e.g. anaemia, renal impairment, hypercalcaemia and lytic bone lesions. Lytic lesions generally occur in the vertebral column, particularly thoracic and lumbar vertebrae. Other commonly involved sites are ribs, pelvic bone, skull, mandible and long bones. Hand and foot bones in general seem protected.1 Here, we describe a MM patient with a rare navicular bone manifestation.
Case A 40-year-old man was referred in 2008 with symptomatic anaemia. Medical history and physical examination showed no significant findings. Positron emission tomography-computed tomography (Pet-Ct) showed multiple lytic bone lesions in vertebrae. Serum immunoelectrophoresis showed a IgG/kappa monoclonality. He was diagnosed with MM, IgG/Kappa isotype, stage 3B, according to the Salmon and Durie staging system. He started first-line therapy with twocycle course of vincristine–doxorubicin–dexamethasone and partial remission was achieved. With second-line two-cycle course of bortezomib–cyclophosphamide– dexamethasone, complete remission was achieved.
He underwent autologous stem cell transplantation (SCT), followed by an allogenic SCT in 2009. He was in remission until 2013, when he complained of a progressive, insidious bone pain which started approximately two weeks previously on his left foot. Magnetic resonance imaging (MRI) was performed for suspected involvement and a lytic lesion in his navicular bone was detected (Figure 1). Histological biopsy from this lesion confirmed localised plasmacytoma (Figure 2). At that time there was no graft failure, and the polymerase chain reaction analysis revealed that hematopoietic cells were of donor origin. In bone marrow examination, morphology showed 3% plasma cells (CD38 positive, kappa positive) and flow cytometry showed 1% plasma cell population with CD38+, CD138+, CD19+, CD56 . Serum and urine immune 1
MD, Hematologist, Erciyes University School of Medicine, Hematology Department, M. Kemal Dedeman Oncology Hospital, Kayseri, Turkey 2 2 MD, Assoc. prof, Erciyes University School of Medicine, Hematology Department, M. Kemal Dedeman Oncology Hospital, Kayseri, Turkey 3 MD, Prof., Erciyes University School of Medicine, Pathology Department, Gevher Nesibe Hospital Kayseri, Turkey 4 MD, Prof., Erciyes University School of Medicine, Hematology Department, M. Kemal Dedeman Oncology Hospital, Kayseri, Turkey Corresponding author: Leylagul Kaynar, M. Kemal Dedeman Oncology Hospital, Hematology Department Kayseri, Melikgazi/Kayseri, Turkey. Email: [email protected]
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Scottish Medical Journal 0(0)
Figure 1. T1 and T2-weighted images of left foot magnetic resonance imaging (MRI) showing 18 mm lytic lesion in navicular bone.
Figure 2. Histopathological analysis of navicular bone biopsy: Hematoxylin and eosin stain at high power (40X) showing atypical plasma cells (a), immunohistochemical staining showing diffuse positive for CD138 (b), cytoplasmic lambda (positive) (c) and cytoplasmic kappa light chains (negative) (d).
electrophoresis showed no M protein, with normal light chain ratio, and immunoglobulin levels were in normal range. Biochemical and blood count tests results were within normal limits but albumin. Some of laboratory
findings included the following: creatinine 93.7 umol/l (1.06 mg/dl), corrected calcium 2.3 mmol/l (9.3 mg/dl), phosphorus 0.7 mmol/l (2.2 mg/dl), total protein 47 g/l (4.7 g/dl), albumin 26 g/l (2.6 g/dl), alkaline
Yildizhan et al. phosphatase 26 U/L, alanine aminotransferase 24 U/L, aspartate aminotransferase 19 U/L, lactate dehydrogenase 284 U/L. WBC was 9.07103/mcl with 60% neutrophils, 27% lymphocytes; platelet count was 148 103/mcl and haemoglobin was 13 g/dl (8.07 mmol/L). He was considered to have limited local progression and he received radiotherapy (45 Gy) on the lesion in the left foot, followed by treatment with lenalidomide (25 mg/day) and dexamethasone. One year later, while still on lenalidomide treatment, MRI showed a new lesion in the first proximal phalanx of the right foot, for which he then also received local radiotherapy (30 Gy). No new lesions were detected afterwards. After 26 cycles of lenalidomide, treatment had to be stopped because of ‘insurance policy’ reasons and the patient was followed up three months without medical intervention. Free light chain ratio has remained normal in serum and in urine, and the patient is still in remission 33 months later.
Discussion MM accounts for about 10% of haematological malignancies and 1.6% of all cancers. Although still considered incurable, current treatment options have led to an increased five-year survival rate up to 45%. Over 30% of the patients survive for more than 10 years after first diagnosis.2–4 With improved survival rates quality of life becomes more important. Lytic lesions in MM affect approximately 60% of all patients at time of presentation and approximately 80–90% at advanced stages of the disease.4,5 Bone pain is a common symptom and often the first manifestation, leading to the diagnosis. It is caused by micro and macro fractures due to destruction of bone. Bone lesions can range from a classic discrete lytic lesion to widespread osteopenia or multiple lytic lesions affecting any part of skeleton, most often the spine, skull and long bones. Foot and hand bones are rarely affected. In the current English literature, a few cases are reported which describe involvement of the foot bones including talus, calcaneus, cuneiform and cuboid bones and we were able to find just one case report on navicular bone.6–12 Most of these reports describe a solitary plasmacytoma. Incidence of solitary plasmacytoma of foot bone has been estimated to be less than 1% and hand involvement about 2.9% in MM.6,13 However, it is unknown whether these rare bone locations correlate with prognosis. Conventional projection radiography is still the standard method for detection of bone lesions in initial staging and follow-up of MM, owing to its high availability and low costs. Indeed, up to 80% of all newly diagnosed patients have detectable bone lesions on conventional radiography.14 However, conventional X-ray
3 ‘skeletal survey’ does not include hands and feet so lesions in these regions are often not noticed. Even using Pet-Ct, foot and hand lesions can easily be missed. The patient we describe in this report had been in remission for four years after the autologous and sequel allogenic SCT. He then relapsed with localised disease in the navicular bone and then in a phalanx in the foot. At the time of this relapse, immunoelectrophoresis and free light chain tests were negative and plasma cells were
A case of multiple myeloma with navicular bone involvement
Scottish Medical Journal 0(0) 1–4 ! The Author(s) 2017 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/0036933017727962 journals.sagepub.com/home/scm
Esra Yildizhan1, Leylagul Kaynar2, Nicolette Tiren1, Ozlem canoz3 and Bulent Eser4
Abstract Multiple myeloma is a haematological disease caused by proliferation of malignant plasma cells in bone marrow. It frequently has lytic bone lesions. However, involvement of the small bones of the hands and feet is extremely rare. We report a unique multiple myeloma patient with first recurrence in navicular bone after allogenic stem cell transplantation.
Keywords Multiple myeloma, navicular bone
Introduction Multiple myeloma (MM) is a neoplastic disorder characterised by malignant proliferation of clonal plasma cells in bone marrow, aberrant production of monoclonal immunoglobulins (paraprotein), and end organ damage, e.g. anaemia, renal impairment, hypercalcaemia and lytic bone lesions. Lytic lesions generally occur in the vertebral column, particularly thoracic and lumbar vertebrae. Other commonly involved sites are ribs, pelvic bone, skull, mandible and long bones. Hand and foot bones in general seem protected.1 Here, we describe a MM patient with a rare navicular bone manifestation.
Case A 40-year-old man was referred in 2008 with symptomatic anaemia. Medical history and physical examination showed no significant findings. Positron emission tomography-computed tomography (Pet-Ct) showed multiple lytic bone lesions in vertebrae. Serum immunoelectrophoresis showed a IgG/kappa monoclonality. He was diagnosed with MM, IgG/Kappa isotype, stage 3B, according to the Salmon and Durie staging system. He started first-line therapy with twocycle course of vincristine–doxorubicin–dexamethasone and partial remission was achieved. With second-line two-cycle course of bortezomib–cyclophosphamide– dexamethasone, complete remission was achieved.
He underwent autologous stem cell transplantation (SCT), followed by an allogenic SCT in 2009. He was in remission until 2013, when he complained of a progressive, insidious bone pain which started approximately two weeks previously on his left foot. Magnetic resonance imaging (MRI) was performed for suspected involvement and a lytic lesion in his navicular bone was detected (Figure 1). Histological biopsy from this lesion confirmed localised plasmacytoma (Figure 2). At that time there was no graft failure, and the polymerase chain reaction analysis revealed that hematopoietic cells were of donor origin. In bone marrow examination, morphology showed 3% plasma cells (CD38 positive, kappa positive) and flow cytometry showed 1% plasma cell population with CD38+, CD138+, CD19+, CD56 . Serum and urine immune 1
MD, Hematologist, Erciyes University School of Medicine, Hematology Department, M. Kemal Dedeman Oncology Hospital, Kayseri, Turkey 2 2 MD, Assoc. prof, Erciyes University School of Medicine, Hematology Department, M. Kemal Dedeman Oncology Hospital, Kayseri, Turkey 3 MD, Prof., Erciyes University School of Medicine, Pathology Department, Gevher Nesibe Hospital Kayseri, Turkey 4 MD, Prof., Erciyes University School of Medicine, Hematology Department, M. Kemal Dedeman Oncology Hospital, Kayseri, Turkey Corresponding author: Leylagul Kaynar, M. Kemal Dedeman Oncology Hospital, Hematology Department Kayseri, Melikgazi/Kayseri, Turkey. Email: [email protected]
2
Scottish Medical Journal 0(0)
Figure 1. T1 and T2-weighted images of left foot magnetic resonance imaging (MRI) showing 18 mm lytic lesion in navicular bone.
Figure 2. Histopathological analysis of navicular bone biopsy: Hematoxylin and eosin stain at high power (40X) showing atypical plasma cells (a), immunohistochemical staining showing diffuse positive for CD138 (b), cytoplasmic lambda (positive) (c) and cytoplasmic kappa light chains (negative) (d).
electrophoresis showed no M protein, with normal light chain ratio, and immunoglobulin levels were in normal range. Biochemical and blood count tests results were within normal limits but albumin. Some of laboratory
findings included the following: creatinine 93.7 umol/l (1.06 mg/dl), corrected calcium 2.3 mmol/l (9.3 mg/dl), phosphorus 0.7 mmol/l (2.2 mg/dl), total protein 47 g/l (4.7 g/dl), albumin 26 g/l (2.6 g/dl), alkaline
Yildizhan et al. phosphatase 26 U/L, alanine aminotransferase 24 U/L, aspartate aminotransferase 19 U/L, lactate dehydrogenase 284 U/L. WBC was 9.07103/mcl with 60% neutrophils, 27% lymphocytes; platelet count was 148 103/mcl and haemoglobin was 13 g/dl (8.07 mmol/L). He was considered to have limited local progression and he received radiotherapy (45 Gy) on the lesion in the left foot, followed by treatment with lenalidomide (25 mg/day) and dexamethasone. One year later, while still on lenalidomide treatment, MRI showed a new lesion in the first proximal phalanx of the right foot, for which he then also received local radiotherapy (30 Gy). No new lesions were detected afterwards. After 26 cycles of lenalidomide, treatment had to be stopped because of ‘insurance policy’ reasons and the patient was followed up three months without medical intervention. Free light chain ratio has remained normal in serum and in urine, and the patient is still in remission 33 months later.
Discussion MM accounts for about 10% of haematological malignancies and 1.6% of all cancers. Although still considered incurable, current treatment options have led to an increased five-year survival rate up to 45%. Over 30% of the patients survive for more than 10 years after first diagnosis.2–4 With improved survival rates quality of life becomes more important. Lytic lesions in MM affect approximately 60% of all patients at time of presentation and approximately 80–90% at advanced stages of the disease.4,5 Bone pain is a common symptom and often the first manifestation, leading to the diagnosis. It is caused by micro and macro fractures due to destruction of bone. Bone lesions can range from a classic discrete lytic lesion to widespread osteopenia or multiple lytic lesions affecting any part of skeleton, most often the spine, skull and long bones. Foot and hand bones are rarely affected. In the current English literature, a few cases are reported which describe involvement of the foot bones including talus, calcaneus, cuneiform and cuboid bones and we were able to find just one case report on navicular bone.6–12 Most of these reports describe a solitary plasmacytoma. Incidence of solitary plasmacytoma of foot bone has been estimated to be less than 1% and hand involvement about 2.9% in MM.6,13 However, it is unknown whether these rare bone locations correlate with prognosis. Conventional projection radiography is still the standard method for detection of bone lesions in initial staging and follow-up of MM, owing to its high availability and low costs. Indeed, up to 80% of all newly diagnosed patients have detectable bone lesions on conventional radiography.14 However, conventional X-ray
3 ‘skeletal survey’ does not include hands and feet so lesions in these regions are often not noticed. Even using Pet-Ct, foot and hand lesions can easily be missed. The patient we describe in this report had been in remission for four years after the autologous and sequel allogenic SCT. He then relapsed with localised disease in the navicular bone and then in a phalanx in the foot. At the time of this relapse, immunoelectrophoresis and free light chain tests were negative and plasma cells were
