Osteolytic lesions: Multiple myeloma or prostate cancer?

Abstract

Multiple myeloma is a cancer which is characterized by proliferation of malignant B-cells and plasma cell infiltration of bone marrow. Lytic lesions are one of its hallmarks, on radiological assessment. We report 2 cases who presented within 1 year to our hospital with bony lytic lesions on CT scan. They were investigated for multiple myeloma; however, there were no further features to suggest this. Both patients were confirmed to have prostate cancer. This is unusual as prostate cancer produces sclerotic lesions (unusual hardening or thickening of the bone).

Introduction

About 80% of patients with multiple myeloma (MM) will develop pathological fractures at some point of their disease and 90% develop lytic bony lesions [1]. Plain radiography, CT, and MRI scans are used to identify these lytic lesions, which could facilitate early intervention—such as, femoral nailing to prevent fractures. The diagnosis of MM requires the presence of Bence Jones protein on urine analysis, assessment of serum-free light chain ratio, presence of a paraprotein on serum protein electrophoresis, and demonstration of plasma cells on bone marrow biopsy. The 2 cases we are reporting here were referred to the hematology team for a possible diagnosis of MM, after the detection of bony lytic lesions on CT. In both cases, the patients had prostate cancer.

Patient 1

Case presentation: A 58-year-old male, with a past medical history of rheumatoid arthritis, who was diagnosed with prostate cancer following an elevated PSA level (992 ug/L) and palpation of a hard mass on the right side of the prostate, on per rectal examination.

Investigations: Bone scan showed an area of increased uptake at the junction of the middle and lower third of the left femoral shaft and X-ray showed no focal sclerosis but a subtle lucency, which was suggestive of metastasis. CT abdomen and pelvis was done which showed bilateral external iliac lymphadenopathy with retroperitoneal lymphadenopathy supporting a diagnosis of metastatic lymphadenopathy secondary to prostate cancer. In addition, multiple lytic deposits were seen throughout the lumbar spine, thoracic spine, and pelvis which were suspicious of metastasis. Due to the extensive lytic lesions seen on radiological examination, the patient was referred to hematology for exclusion of MM. He had normal full blood count, normal calcium levels, normal creatinine levels, and normal lactate dehydrogenase (LDH) levels. The serum protein electrophoresis demonstrated no visible paraprotein and no immune paresis, with entirely normal IgG, IgA, and IgM levels. The serum free light chain analysis also demonstrated normal levels with normal Kappa to Lambda ratio of 1.22. A bone marrow biopsy was performed and showed a trilineage hemopoietin marrow with 2 small nests of nonhematological cells that were PSA +ve. The presence of these cells supported the diagnosis of metastatic prostate cancer in the bone marrow.

Outcome and follow-up: Patient 1 was diagnosed with prostate cancer, and he was started on hormonal treatment.

Patient 2

Case presentation: Patient 2 was a 92-year-old male known to have hypertension, gout, chronic kidney disease, sciatica, and under monitoring for prostate cancer since 2019 (with low PSA levels). He was recently diagnosed with unprovoked extensive left leg proximal deep vein thrombosis. He was started on rivaroxaban and referred to the hematology team. Due to the COVID-19 pandemic, the patient had telephone consultation at the hematology clinic and reported severe back pain with significant swelling in the right leg and scrotum.

Investigations: A CT scan of the chest, abdomen, and pelvis showed para-aortic soft tissue mass around the infrarenal abdominal aorta, lytic lesions within the pelvis, and multiple lytic lesions in L4 and L5 vertebral bodies causing spinal compression. The PSA remained mildly elevated at 24 ug/L (normal 0-15 ug/L.) He had normal full blood counts, normal bone profile, and serum electrophoresis. Bence jones protein was not detected. The patient was subsequently admitted due to worsening back pain. The outcome from the multidisciplinary team meeting was not to perform a biopsy on the abdominal mass because of the risk of damage to surrounding blood vessels. Instead, a blind bone marrow biopsy was recommended; given that the pelvis had extensive lytic lesions. The bone marrow trephine sample was normal except a 1% CD5+ clonal cell which is likely to be an incidental finding. The patient underwent a CT-guided biopsy of the right iliac fossa.

Outcome and follow-up: The bone sample showed evidence of metastatic carcinoma, likely prostate carcinoma. Patient declined hormonal treatment for prostate cancer and was transferred to a hospice for palliative treatment.

Differential diagnosis: The differential diagnosis for the lytic lesions in both cases was MM and bony metastasis from prostate carcinoma.

Figs. 1 and 2 show lytic lesions on CT scan for Patient 1 and Patient 2, respectively. Fig. 3 shows increased FDG uptake on PET-CT scan for Patient 1.

Fig 1.

Multiple lytic deposits throughout the lumbar and visualized thoracic spine.

Fig 2.

Multiple lytic lesions seen for example in L4-L5 vertebral bodies.

Fig 3.

PET-CT for patient 1 shows increased FDG uptake at the sites of lytic lesions.

Discussion

MM is defined as malignant proliferation of B cells. It accounts for 15% of hematological malignancies and 2% of all cancers [2]. The common features of MM include hypercalcemia, renal impairment, anemia, and bony involvement with hallmark lytic lesions. The bony involvement seen in MM includes widespread osteopenia, classic discrete lytic lesions, and fractures, which has a significant role in increasing the morbidity of the disease. Increased osteoclastic destruction in areas of myeloma proliferation and decreased activity of osteoblasts produces osteolytic lesions [2]. MM is particularly difficult to diagnose, partially due to nonspecific presenting features; with back pain being the most common presenting complaint.

One or more lytic bone lesions seen on skeletal radiography, CT or positron emission tomography computed tomography (PET-CT) (>5 mm in size) is consistent with a myeloma-defining event. An increased uptake on PET-CT without lytic lesion does not meet the criteria for diagnosing MM but is associated with increased risk of progression to myeloma. Repeat imaging must be performed if there is any doubt regarding equivocal or lucencies measuring <5 mm. Furthermore, bony lesions should be biopsied if there are concerns about bony metastases [4].

Prostate cancer is the most common cancer affecting men. The incidence of a man being diagnosed with prostate cancer during a lifetime is 1 in 7 in the United States and 1 in 25 worldwide [5]. Hematogenous spread of malignant cells has a predilection to metastasize to axial bones such as ribs, pelvis, and spine (areas where red marrow is prevalent [6]). This is similar to MM, where lytic lesions are seen in the axial skeleton. Lytic lesions in prostate cancer are extremely rare [7].

Both patients presented with an uncommon radiological finding of prostate cancer (diffuse osteolytic metastases). The main differential diagnosis for the lytic lesions in both cases was MM and bony metastasis from prostate carcinoma. The need to investigate for a possibility of a second malignancy in patient 1 and the assumption that the prostate cancer was not active in patient 2, led to the hematology referral. Appropriate investigations should be done to further evaluate the possibility of MM (as per Table 1). However, in the interest of time, some of these investigations like blood and urinary tests can be arranged by the referring teams, rather than referring to the hematology team. Especially, as there are a greater number of cases of lytic lesions secondary to malignancies (other than MM) being reported.

Table 1.

The diagnostic criteria for MM adapted from International Myeloma Working Group Updated Criteria [3].

Multiple myeloma: (both criteria must be met)
1. Clonal bone marrow plasma cells ≥10% or biopsy proven plasmacytoma
2. One or more myeloma-defining events:	[S] ≥60% plasma cells in marrow [LI] Kappa:Lambda ratio ≥100 or ≤0.01 [M] 2 or more focal lesions on MRI (>5 mm in size) [C] Hypercalcemia: (>2.75 mmol/l or >0.25 mmol/l higher than upper limit of normal) [R] Renal insufficiency: (serum creatinine >177 µmol/l or creatinine clearance <40 ml/min) [A] Anemia: Hb <100 g/l or 20 g/l below lower limit of normal [B] 1 or more lytic bone lesion on X-ray, CT or PET-CT (>5 mm in size)

A case study reported by Sharma et al. [8] involved a 62-year-old man who presented with low-grade fever for 3 months. The patient had multiple lytic lesions on plain radiograph which were suspicious of metastases. Subsequently, PET-CT was done which revealed multiple lytic lesions, enlarged prostate gland and retroperitoneal lymph nodes. PSA levels were raised (360 ng/ml.) Bone marrow biopsy was done to rule out other malignancy, which confirmed the diagnosis of metastatic prostate carcinoma. The report states that 18 fluorine fluorodeoxyglucose PET-CT is useful in making the primary diagnosis of prostate cancer in patients with lytic skeletal metastasis.

Another case study by Idowu [9] included a 66-year-old man who presented with left supraclavicular swelling, poor urinary stream, and low pain back for 5 months. Blood results were normal—no cytopenia, hypercalcemia, Bence jones proteinuria; however, PSA levels were elevated (16 ng/mL). Plain radiographs showed diffuse osteolytic lesions. CT abdomen and pelvis showed retroperitoneal adenopathy, in addition to enlarged prostate and diffuse lytic bone lesions. Serum protein electrophoresis was normal (no M band.) Bone marrow aspiration was normal - plasma cells constituted 1% of bone marrow cells with a normoblastic picture. A diagnosis of metastatic prostate cancer was made.

An interesting case reported by Segamwenge et al. [10] involved a 65-year-old male who presented with anemia, thrombocytopenia, worsening back pain, dysuria, and mild symptoms of bladder outlet obstruction. Diffuse osteolytic lesions were seen in the right humerus, all vertebrae, femur and pelvic bones. This is particularly interesting as he had symptoms of MM such as anemia and back pain but the investigations for myeloma were negative. PSA was raised and prostate biopsy confirmed prostate cancer.

Diffuse osteolytic metastases mimicking myeloma has also been reported in patients with hepatocellular carcinoma and breast cancer, therefore high levels of suspicion should be maintained [11,12].

Conclusion

• •We report 2 cases, within 1 year, who presented with lytic lesions on radiological assessment but did not have evidence of multiple myeloma.
• •This highlights that patients who present with osteolytic lesions should not only be investigated for myeloma but also for other malignancies; with prostate cancer being an important differential diagnosis in men.

Patient consent

Verbal and written informed consent were obtained for the publication of this case report, including accompanying images and case history.