Computed tomography characteristics of multiple myeloma and other osteolytic metastatic bone lesions

Abstract

Background

Differentiation of multiple myeloma (MM) from osteolytic metastatic (OM) bone lesions may be critical in patients with lytic bone lesions but can be challenging for radiologists.

Purpose

To determine whether computed tomography (CT) can be used to distinguish between MM and other OM bone lesions.

Material and Methods

In this retrospective study, 320 lesions of 207 patients diagnosed with MM or OM, based on biopsy or clinical examination, were evaluated. Eight qualitative features were evaluated by two radiologists blinded to the diagnoses. The chi-square and Fisher exact tests, and logistic regression analysis, were used to evaluate the relationships between the CT findings and diagnoses.

Results

High-density areas were more common in OM than MM lesions (85.2% and 19%, P < 0.001), as were perilesional sclerosis (38.9% vs. 13.2%, P < 0.001), heterogeneity (on non-contrast CT images, 60% vs. 19.1%, P < 0.001; on contrast enhanced CT images, 80.6% vs. 28.2%, P < 0.001), and ill-defined margins (34.6% vs. 9.1%, P < 0.001). Similarly, OM lesions showed high-density areas more than MM in evaluation of skeletal system subgroups (vertebrae, 93.8% vs. 29.8%, P < 0.0001; thoracic cage bones, 69.6% vs. 19.2%, P < 0.001; pelvic bones and sacrum, 84.8% vs. 7.7%, P < 0.001; peripheral skeletal bones, 81.5% vs. 8.3%, P < 0.001). Logistic regression analysis revealed that the presence of a high-density area in the lesion increased the probability of a metastasis 25.88-fold (R² = 0.516, P < 0.001).

Conclusion

MM and OM lesions can be differentiated by CT; OM lesions exhibit high- density areas.

Keywords

Multiple myeloma osteolytic metastatic bone lesions computed tomography computed tomography characteristics

Introduction

Multiple myeloma (MM) is a plasma cell disorder characterized by uncontrolled proliferation of a clone of plasma cells within the bone marrow, production of a monoclonal immunoglobulin, and end-organ damage (1 –3). MM frequently shows skeletal system involvement (4). Of all patients with MM, 70%–80% exhibit lytic bone lesions at diagnosis and approximately 90% develop such lesions during the course of disease (5,6).

The skeleton is commonly affected in patients with metastatic cancers, particularly breast and prostate cancers (7,8). Bone metastases may be osteoblastic, osteolytic, or mixed, affecting both bone remodeling and radiographic appearance (7). Osteolytic metastases are characterized by high-level bone destruction with little new bone formation, commonly accompanied by breast, lung, and kidney tumors (9,10).

Many case reports have shown that MM may develop as a secondary neoplasia in patients with a known primary malignancy. Tomono et al. (11), Chandra et al. (12), Hingmire et al. (13), and Hough et al. (14) published case reports on MM-induced lytic bone lesions developing during the follow-up of patients with breast cancer. Therefore, new bone lesions in patients with cancer should be investigated carefully; early and specific treatment is critical in terms of prognosis and survival (12,15). Accurate diagnosis is essential and radiological examination plays a crucial role in distinguishing MM from metastases (12).

MM bone involvement is typically characterized by uncoupled or severely imbalanced bone remodeling. MM and other metastatic bone tumors exhibit increased bone resorption; however, osteoblast activity is either suppressed or absent in MM bone lesions (5,16). In osteolytic metastases, the mechanisms affecting tumor development are complex, involving both osteoblast stimulation and increased osteoclastic activity, unlike MM (17).

Significant suppression of osteoblastic activity by MM bone tumors seems to be the most important difference between MM and other osteolytic metastatic (OM) lesions. Early diagnosis greatly improves the prognosis of patients with osteolytic lesions, and it is important to distinguish between MM and OM lesions.

The aim of the present study was to use computed tomography (CT) to this end, especially to identify high-density lesion areas that might reflect new bone formation or preservation of the trabecular structure.

Material and Methods

Patients

We retrospectively evaluated the CT images of patients diagnosed with MM or OM from 2007 to 2019 in the Radiology Department of our University Hospital. The inclusion criteria for patients with MM were as follows: (i) MM diagnosed according to the criteria of the International Myeloma Working Group; (ii) a plasma cell disorder diagnosed via bone or bone marrow biopsy; (iii) availability of CT images obtained for any reason before any treatment; and (iv) at least one evaluable bone lesion on a CT image. The inclusion criteria for the patients with OM were as follows: (i) a CT image obtained either at diagnosis or during follow-up that included at least one lytic bone lesion; (ii) absence of any treatment when the CT scan was obtained; and (iii) diagnosis of a metastasis either pathologically or based on clinical and laboratory data. Patients who received treatment or lacked lytic bone lesions were excluded; treatment could affect the CT characteristics

A radiologist who was not otherwise involved in the study selected CT images based on the above criteria. All CT examinations of patients with MM, and the examinations of 59 of 117 patients with OM, had been performed before diagnosis to evaluate various clinical symptoms and indications, either in association or not in association with MM or OM. These patients who had lytic lesions but had not yet been diagnosed were diagnosed with MM or OM. The CT images of patients with OM who lacked lytic lesions at diagnosis but exhibited them on arterial and portal phase follow-up thoracoabdominal CT images were included.

We evaluated cranial, spinal, pelvic bone, extremity, thoracic, and abdominal CT scans. Although some patients did not undergo all of these CT examinations, they all completed one or more clinically indicated CT evaluation and met the study inclusion criteria. CT images were obtained using the Aquilion Prime 160-channel instrument (Toshiba Medical Systems, Otawara, Japan) or the Brilliance (16- or 64-channel) instrument (Phillips Healthcare, Best, The Netherlands). Slice thickness was in the range of 1–3 mm. If necessary, multiplanar reconstruction of the original axial planes was performed. All lesions were evaluated at the optimal CT window level.

The study was approved by the institutional ethics committee in January 2019.

Assessment of CT images

CT images were assessed by two radiologists, with three and 20 years of experience in skeletal radiology, blinded to the diagnoses. Eight qualitative features were analyzed: (i) high-density areas (evaluated visually) potentially associated with a preserved trabecular structure or new bone formation, including linear, dotted, and amorphous areas (Fig. 1); (ii) perilesional sclerosis (a sclerotic area around some or all of the lesion, but not normal bone; Fig. 2); (iii) marginal features (ill-defined or sharp margins); (iv) bone expansion; (v) accompanying soft tissue; (vi) cortical destruction; (vii) lesion homogeneity or heterogeneity; and (viii) pathological fractures (Figs. 3 –5). Internal features of the lesions were separately evaluated on contrast-enhanced and non-enhanced scans. If more than one lesion was evident, the largest lesion was assessed. However, if the largest lesion lacked a fracture, a lesion with a fracture was assessed instead. The skeletal system was divided into the skull, the vertebrae (cervical, thoracic, and lumbar), the pelvic region (ilium, ischium, pubis, and sacrum), the thoracic cage (ribs, sternum, scapula, and clavicle), and the peripheral region. If a patient exhibited lesions in more than one of these areas, all areas were evaluated. Multiple lesions that could not be clearly distinguished were classified as “diffuse involvement” and only fractures were checked for. Marginal and internal features could not be accurately assessed in such lesions. All of the CT data analyzed were obtained by the senior investigator.

Fig. 1.

Linear and dotted high-density lesion areas potentially reflecting a preserved trabecular structure or new bone formation are observed in the lesion (white arrow).

Fig. 2.

(a, b) In both left (a) and right (b) images, lytic lesions showing a sclerotic area around (black and white arrow) are observed. Both were diagnosed with osteolytic metastatic lesions.

Fig. 3.

(a, b) Ill-defined lytic iliac bone lesion (black and red arrows). The lesion cannot be distinguished from normal bone tissue on both bone and soft-tissue window levels. (c, d) Sharp-edged lytic vertebrae lesion (white and blue arrows). The lesion can be easily differentiated from normal bone tissue.

Fig. 4.

(a) A lytic pelvic bone lesion (black arrows) presenting with cortical destruction is seen on CT image of the patient diagnosed with renal cell carcinoma. The lesion shows no soft-tissue component. In addition, linear and dotted high-density areas can be observed. (b) A lytic proximal humerus lesion presenting with soft-tissue component, cortical destruction, and bone expansion is seen on non-contrast CT image. CT, computed tomography.

Fig. 5.

(a) A lytic “heterogeneous” iliac lesion is seen on abdominal contrast-enhanced CT image of the patient diagnosed with renal cell carcinoma. (b) On abdominal contrast-enhanced CT image of the patient diagnosed with MM, a lytic sacral lesion presenting with “homogenous” internal feature is observed. CT, computed tomography; MM, multiple myeloma.

Statistical analysis

Data were analyzed using SPSS software (ver. 22.0; SPSS, Inc., Chicago, IL, USA). Standard descriptive summary statistics were used to show trends. The chi-square and Fisher exact tests, and logistic regression analysis, were employed to explore the relationships between CT findings and diagnosis. Kappa analysis was used to assess inter-observer reliability. A P value < 0.05 was considered to reflect statistical significance.

Results

We evaluated 207 CT images of patients who met the study inclusion criteria; 90 were diagnosed with MM and 117 with OM. Sixty-eight patients with OM were men and 49 were women (mean age = 58.80 ± 13.2 years; age range = 22–85 years). Sixty-two patients with MM were men and 28 were women (mean age = 59.99 ± 9.92 years; age range = 33–81 years). The primary diagnoses of the patients with OM are listed in Table 1.

Table 1.

The primary diagnosis of patients with osteolytic metastatic lesions.

Diagnosis	Patients (n)
Lung cancer	33
Breast cancer	27
Renal cell carcinoma	12
Gastric cancer	6
Thyroid cancer	5
Prostate cancer, lymphoma	3
Neuroendocrine tumor, cervical cancer, urothelial carcinoma, synovial sarcoma	2
Paraganglioma, leiomyosarcoma, endometrial carcinoma, hepatocellular carcinoma, salivary gland tumor, esophageal cancer, malign melanoma, colon cancer, mesothelioma, bladder cancer, laryngeal cancer, soft tissue sarcoma	1
Metastasis of unknown origin	8
Total	117

As mentioned above, the lesions were evaluated in all skeletal bone subgroups; we studied 320 lesions in 207 patients. Thirty-seven lesions of 16 patients exhibited diffuse involvement; 15 patients had MM lesions and one had an OM lesion, all of which were evaluated only in terms of fracture. The remaining 283 lesions were assessed in all respects; 162 lesions were OM and 121 were MM.

Overall, high-density lesion areas were more common in patients with OM than in patients with MM (85.2% and 19.0%; P < 0.001; Table 2, Fig. 6); this was also the case for all skeletal system subgroups (vertebrae, 93.8% vs. 29.8%, P < 0.0001; thoracic cage bones, 69.6% vs. 19.2%, P < 0.001; pelvic bones and sacrum, 84.8% vs. 7.7%, P < 0.001; peripheral skeletal bones, 81.5% vs. 8.3%, P < 0.001; Table 3). Overall, perilesional sclerosis was more common in OM lesions than in MM lesions (38.9% vs. 13.2%, P < 0.001; Table 2, Fig. 7): this was also the case for two of the skeletal system subgroups (vertebrae, 67.7% vs. 27.7%, P < 0.0001; pelvic bones, 26.1% vs. 3.8%, P = 0.024). Overall, ill-defined margins were more common in OM lesions than in MM lesions (34.6% vs. 9.1%, P < 0.001; Table 2); this was also the case in the thoracic cage bone skeletal subgroup (43.5% vs. 11.5%, P = 0.011). In our study, all MM lesions of pelvic and peripheral skeletal bones exhibited sharp margins. However, this was 67.4% and 51.9% for pelvic bones and peripheral skeletal bones of OM lesions, respectively. 32.6% of pelvic bones and 48.1 % of peripheral skeletal bones of OM lesions showed ill-defined margins. The internal features of lesions were separately evaluated on contrast-enhanced and non-enhanced scans. In both scan types, OM lesions were significantly more heterogeneous than MM lesions. On non-contrast CT scans, 60% and 19.1% of OM and MM lesions were heterogeneous, respectively (P < 0.001). On contrast-enhanced scans, the respective values were 80.6% and 28.2% (P < 0.001; Table 4). In terms of vertebral lesions, OM lesions were significantly more heterogeneous than MM lesions on both contrast-enhanced and non-enhanced scans (80% vs. 33.3%, P = 0.009 and 70% vs. 25.7%, P < 0.001, respectively).

Table 2.

Data on the evaluation of CT characteristics of MM lesions and metastatic lesions.

		MM	OM	P value
The presence of high-density (bone-like density) areas	Positive	23 (19)	138 (85.2)
	Negative	98 (81)	24 (14.8)
				<0.001
Cortical destruction	Positive	100 (82.6)	149 (92)
	Negative	21 (17.4)	13 (8)
				0.017
Bone expansion	Positive	72 (59.5)	108 (66.7)
	Negative	49 (40.5)	54 (33.3)
				0.215
Soft-tissue component	Positive	58 (47.9)	96 (59.3)
	Negative	63 (52.1)	66 (40.7)
				0.058
Perilesional sclerosis	Positive	16 (13.2)	63 (38.9)
	Negative	105 (86.8)	99 (61.1)
				<0.001
Margin features	Sharp	110 (90.9)	106 (65.4)
	İll-defined	11 (9.1)	56 (34.6)
				<0.001

Values are given as n (%) unless otherwise indicated. A statistically significant data, p value less than 0.05, were shown in bold in all tables. Bold font was used to emphasis statistically significant difference observed in evaluating a variable.

CT, computed tomography; MM, multiple myeloma.

Fig. 6.

(a) “High-density area” (dark arrow) in the lytic vertebrae bone lesion is seen on spinal CT image of a 50-year-old woman diagnosed with breast cancer. (b) On a pelvic bone CT image, there is a lytic lesion located in the femur neck. The blue arrow shows “high-density areas” in the lesions. The patient was diagnosed with diffuse large B-cell lymphoma by biopsy. (c) and (d) CT images of patients with MM. Both lesions are purely lytic and show no “high-density areas.” CT, computed tomography; MM, multiple myeloma.

Table 3.

Data on the evaluation of the presence of high-density (bone-like density) areas in the skeletal system subgroups.

	The presence of high density (bone-like density) areas in the lesion
	MM		OM
	Positive	Negative	Positive	Negative	P value
Vertebrae	14 (29.8)	33 (70.2)	61 (93.8)	4 (6.2)	<0.001
Thoracic cage bones	5 (19.2)	21 (80.8)	16 (69.6)	7 (30.4)	<0.001
Pelvic region bones	2 (7.7)	24 (92.3)	39 (84.8)	7 (15.2)	<0.001
Peripheral skeletal system	1 (8.3)	11 (91.7)	22 (81.5)	5 (18.5)	<0.001
Cranium	1 (10)	9 (90)	0	1 (100)	*

*There were not enough lesions to perform a statistical analysis.

MM, multiple myeloma; OM, osteolytic metastases.

Fig. 7.

Abdominal CT image of a 61-year-old woman diagnosed with cervical cancer: a lytic vertebrae lesion showing a sclerotic area around the lesion (black arrow) is seen. In addition, high-density areas in the lesion are observed. (blue arrow).

Table 4.

Data on the evaluation of lesions internal structure on non-contrast and contrast-enhanced CT examinations.

		MM	OM
Lesion internal feature on non-contrast CT images	Homogenous	72 (80.9)	36 (40)
	Heterogeneous	17 (19.1)	54 (60)
				<0.001
Lesion internal feature on contrast-enhanced CT images	Homogenous	23 (71.8)	14 (19.4)
	Heterogeneous	9 (28.2)	58 (80.6)
				<0.001

CT, computed tomography; MM, multiple myeloma; OM, osteolytic metastases. A statistically significant data, p value less than 0.05, were shown in bold in all tables. Bold font was used to emphasis statistically significant difference observed in evaluating a variable.

Although an accompanying soft-tissue component and bone expansion were more common in OM lesions than in MM lesions, the difference was not significant. Soft-tissue components were evident in 59.3% of OM lesions and 47.9% of MM lesions (P = 0.058). Of all OM lesions, 66.7% were associated with cortical expansion compared to 59.5% of MM lesions (P = 0.215).

Cortical destruction was observed in most OM and MM lesions (92% and 82.6%, respectively, P = 0.017); the skeletal subgroup figures did not differ significantly. Pathological fractures were evaluated in all lesions, including those exhibiting diffuse involvement; fractures were observed in 27.4% and 35.3% of OM and MM lesions, respectively (P = 0.148).

We used logistic regression analysis to evaluate the relationship between qualitative lesional characteristics and diagnosis. The presence of a high-density area increased the overall probability of OM lesions (by 25.88-fold; odds ratio [OR] = 25.88, 95% confidence interval [CI] = 13.73–48.75, R² = 0.516, P < 0.001), and lesions involving the vertebrae, thoracic cage, and pelvic bones (OR = 26.9, 95% CI = 7.86–92.10, R² = 0.535, P < 0.001; OR = 32.34, 95% CI = 2.96–353.72, R² = 0.676, P = 0.004; and OR = 41.14, 95% CI = 7.74–218.61, R² = 0.657, P < 0.001, respectively). On contrast-enhanced CT, heterogeneity increased the probability of an OM lesion (OR = 6.36, 95% CI = 2.04–19.97, R² = 0.512, P = 0.001). No other significant relationship was noted. Kappa analysis was used to evaluate inter-observer reliability. For most parameters, reliability was excellent, although that for internal features of lesions was moderate and that for marginal features was good (Table 5).

Table 5.

Assessment of inter-observer reliability.

	Kappa value*
The presence of high-density (bone-like density) areas in the lesion	0.88
Cortical destruction	0.86
Bone expansion	0.83
Accompanying soft-tissue component	0.84
Perilesional sclerosis	0.88
Margin features	0.74
Lesion internal structure	0.56

*< 0.20 = poor; 0.20–0.39 = fair; 0.40–0.59 = moderate; 0.60–0.79 = good; > 0.80 = excellent. Bold values indicate statistically significant data, p value less than 0.05. Bold font is used to emphasize statistically significant difference observed in evaluating a variable.

Discussion

The principal finding of this study was that the presence of high-density areas may distinguish MM from OM lesions. As mentioned above, MM is characterized by increased osteoclast activity and osteoblast inhibition (18). In osteolytic metastases, the mechanisms affecting tumor development are complex, involving both osteoblast stimulation and increased osteoclastic activity (17). Thus, we expected that high-density areas, which might represent new bone formation or residual bony tissue, would be more common in OM lesions than in MM lesions; this was supported by the results. No prior radiological study has explored this topic. However, a palaeopathological study found no new bone in MM lesions; also, the trabecular structure was not preserved. Both preserved trabeculation and residual cortical foci were observed in OM lesions (19). MM lesions are essentially lytic in nature and are not involved in reactive bone formation (3). The fact that high-density areas are more common in OM lesions than in MM lesions may reflect differences in the pathological mechanisms, but additional studies are needed to confirm this.

Perilesional sclerosis was more common in patients with OM than in patients with MM. Bratu et al. (20) found that about 16% of bone metastases exhibited sclerotic rims on magnetic resonance (MR) images. We observed perilesional sclerotic areas in some metastatic lesions. Bratu et al. also noted that hematological bone lesions were homogeneous and lacked surrounding rims. Perilesional sclerosis may be associated with an osteoblastic response of normal bone tissue adjacent to the lesion. However, there are currently no data to support this. Perilesional sclerosis was more common in the vertebral and pelvic bones of our patients with OM compared to those with MM but did not differ among other skeletal bones. Vertebral and pelvic bones are wider than the bones of the thoracic cage, cranium, and peripheral skeleton; therefore, perilesional sclerosis may be more apparent in the former types of bones, which could explain the differences observed in this study. In addition, perilesional sclerosis can be observed in some benign bone lesions. Thick and sclerotic layers can be seen around spinal fibrous dysplasia lesions. Also, osteoblastoma, which may sometimes present with aggressive features like cortical disruption or soft-tissue component, can show variable degree sclerosis around the lesion. Overlaps like perilesional sclerosis between the characteristics of malign and benign bone lesions may make differential diagnosis challenging (21).

Bone expansion and soft-tissue component was more common in OM lesions than in MM lesions, but the difference was not significant. Soft-tissue components were more common in MM lesions than in metastatic vertebral lesions but, again, not significantly. Huh et al. (22) aimed to differentiate spinal MM from metastatic lesions in sagittal MR images; paravertebral mass formation was more common in the latter lesions, in contrast to our findings. Lee et al. (23) found that, on MR images, paraspinal and epidural masses were more common in metastatic lesions than in MM lesions (51% vs. 36%; P > 0.05), again in contrast to our findings. However, both studies used MR images, which are more suitable for evaluating soft tissues than CT images. This may explain the differences between the studies.

The MM lesions in our study tended to be more sharp-edged than metastatic lesions. However, most of the OM lesions were also somewhat sharp-edged. Huh et al. (22) showed that focal lesional margins were distinct in most patients with MM (8/10, 80%) and indistinct in most patients with OM (16/21, 76.2%). Although no significant difference in vertebral lesions was evident, the OM lesions in thoracic cage and pelvic bones in this study, and in the peripheral skeletal system, were significantly more likely to be ill-defined than the MM lesions. In these three skeletal subgroups, soft-tissue components were more common in OM lesions. Extension into soft tissue may explain why OM lesions are less defined than MM lesions. CT is not ideal for evaluating soft tissue. Also, thoracic cage bones exhibit a higher cortical-to-trabecular bone ratio than the vertebrae, and so may be more sharp-edged.

The only independent variables exhibiting moderate inter-observer reliability were the internal features of the lesions; quantitative evaluation of attenuation differences might have enhanced reliability. Also, the kappa values of the non-contrast-enhanced CT images were lower than those of the contrast-enhanced images; evaluation of internal features on unenhanced images may have been challenging. MM lesions evident on post-contrast T1-weighted MR images generally exhibit homogeneous enhancement (3,24). Bratu et al. (20) considered such enhancement suspicious of bone metastasis. We also found that MM lesions tended to be more homogeneous on contrast-enhanced CT. Metastatic lesions may be more heterogeneous in appearance because of hemorrhage or necrosis, although pathological evidence for this is lacking.

The present study had some limitations. First, although all patients with MM were biopsied, biopsy-proven results were available for only 59 of the 117 patients with OM; the others were diagnosed on the basis of clinical and laboratory data. In addition, CT images were only visually assessed; no measurements were performed. Further, only the largest lesions were evaluated. If MM and OM were both present, the assessment may have been inaccurate.

In conclusion, we found that the presence of a high-density area in the lesion may represent new bone formation or preserved trabecular structure and could be used to distinguish metastatic from MM lesions. Lesional homogeneity, perilesional sclerosis, and marginal features may facilitate discrimination. No previous study has compared the CT features of MM and OM lesions. As CT is commonly used, our data are important, although additional studies are required.

Footnotes

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

ORCID iD

Uygar Mutlu

Hakan Abdullah Özgül

References

Hameed

Brady

Dowling

, et al. Bone disease in multiple myeloma: pathophysiology and management. Cancer Growth Metastasis 2014; 7:33–42.

Amos

Agarwal

Kanekar

Imaging of multiple myeloma. Hematol Oncol Clin N Am 2016; 30:843–865.

Collins

CD.

Multiple myeloma. Cancer Imaging 2004; 4:47–53.

Roodman

GD.

Pathogenesis of myeloma bone disease. J Cell Biochem 2010; 109:283–291.

Roodman

GD.

Pathogenesis of myeloma bone disease. Leukemia 2009; 23:435–441.

Terpos

Dimopoulos

Moulopoulos

AL.

The role of imaging in the treatment of patients with multiple myeloma in 2016. Am Soc Clin Oncol Educ Book 2016; 35:e407–417.

Coleman

RE.

Metastatic bone disease: clinical features, pathophysiology and treatment strategies. Cancer Treat Rev 2001; 27:165–176.

Heindel

Gübitz

Vieth

, et al. The diagnostic imaging of bone metastases. Dtsch Arztebl Int 2014; 111:741–747.

Vassiliou

Kalogeropoulou

Petsas

, et al. Clinical and radiological evaluation of patients with lytic, mixed and sclerotic bone metastases from solid tumors: is there a correlation between clinical status of patients and type of bone metastases? Clin Exp Metastasis 2007; 24:49–56.

10.

Nayır

Pathogenesis of bone metastasis. Journal of Oncological Science 2016; 1:13–16.

11.

Tomono

Fujioka

Kato

, et al. Multiple myeloma mimicking bone metastasis from breast cancer: report of a case. Surg Today 1998; 28:1304–1306.

12.

Chandra

Verma

SK.

Multiple myeloma or metastatic carcinoma breast: diagnostic dilemma in a case presenting with lytic bony lesion. Breast Dis 2015; 35:199–201.

13.

Hingmire S, Hingmere S, Bakshi A, et al. Multiple myeloma mimicking bone metastasis in a patient of carcinoma breast. Indian J Med Paediatr Oncol 2008; 29:53–55.

14.

Hough

Brufsky

Lentzsch

Metastatic breast cancer or multiple myeloma? Camouflage by lytic lesions. J Oncol 2010; 2010:509530.

15.

Zhang Ha, Jurong LV, Chaoliang LV, et al. Presentation of multiple myeloma mimicking bone metastasis from colon adenocarcinoma: a case report and literature review. Mol Clin Oncol 2016;4:31–34.

16.

Giuliani

Rizzoli

Roodman

GD.

Multiple myeloma bone disease: patho-physiology of osteoblast inhibition. Blood 2006; 108:3992–3996.

17.

Sanchez

Sistal

AG.

A quantitative method for the characterization of lytic metastases of the bone from radiographic images. Scientific World Journal 2014; 2014:264836.

18.

Terpos

Ntanasis-Stathopoulos

Gavriatopoulou

, et al. Pathogenesis of bone disease in multiple myeloma: from bench to bedside. Blood Cancer J 2018; 8:7.

19.

Rothschild

Hershkovitz

Dutour

Clues potentially distinguishing lytic lesions of multiple myeloma from those of metastatic carcinoma. Am J Phys Anthropol 1998; 105:241–250.

20.

Bratu

Raica

Salcianu

, et al. MRI differential diagnosis: bone metastases versus bone lesions due to malignant hemopathies. Rom J Morphol Embryol 2017; 58:1217–1228.

21.

Albano

Messina

Gitto

, et al. Differential diagnosis of spine tumors: my favorite mistake. Semin Musculoskelet Radiol 2019; 23:26–35.

22.

Huh

Yoon

Kim

, et al. Differentiation of multiple myeloma and metastasis: emphasis on bone marrow involvement pattern of spine in sagittal MR images. J Korean Radiol Soc 1999; 40:769–775.

23.

Lee

Jee

, et al. MR distinction between multiple myeloma and metastasis involving the spine. J Korean Radiol Soc 2001; 44:229–235.

24.

Meletios

Moulopoulos

Datseris

, et al. Imaging of myeloma bone disease - implications for staging, prognosis and follow-up. Acta Oncol 2000; 39:823–827.