Advanced myeloma masquerading as chronic shoulder pain in a 48-year-old man: a diagnostic dilemma

Abstract

Although solitary plasmacytomas may occasionally present as collar bone swellings or fractures, multiple myeloma involving clavicle is extremely rare. Ten to forty per cent of multiple myeloma cases are asymptomatic and are incidental diagnoses. Our case report describes an entirely benign presentation like chronic shoulder pain masquerading advanced myeloma, thereby posing a significant diagnostic dilemma. We present a 48-year-old man who presented with chronic bilateral shoulder pain with no history of trauma and was eventually diagnosed with advanced multiple myeloma and pathologic fracture of the right clavicle. It is, therefore, evident that a low threshold for suspicion can lead to early diagnosis and initiation of treatment and better survival.

Background

Myeloma bone disease (MBD) lesions can present as discrete lytic lesions (radiolucent plasmacytomas) or as widespread osteopenias, multiple lytic lesions predominantly affecting the skull, spine, pelvis, ribs and sternum.¹ The spine is frequently involved; other common sites include long bones (proximal portions of the humerus and femur). Clavicular involvement has been rarely reported in multiple myeloma (MM). Bone pain in myeloma has been classically described as back pain (particularly the lower back), and occasional chest wall pain secondary to the involvement of the ribs and the chest wall.^{1 2} Chronic shoulder pain secondary to nerve compression or pathological fracture in MM is not easily distinguishable from benign unsuspecting shoulder pain and may not raise the alarm for an underlying malignancy. This can pose a diagnostic dilemma for the physician, a probability of diagnosis getting missed, and worse, a progression of underlying malignancy.

Case presentation

A 48-year-old African–American man with no significant past medical history presented to the emergency room with insidious onset bilateral shoulder joint stiffness and pain, occasionally radiating to the neck, bilateral flanks as well as upper arms. On further questioning, he endorsed some fatigue and generalised weakness over some time. Also, there were associated with numbness and tingling in both his hands. A small bony prominence was present on the right clavicle, which, when asked, was present for some time (not accurately quantifiable) before the presentation. No pain was elicited over the bony prominence. No history of trauma was present. On the physical examination, both active and passive ranges of motion of the shoulder elicited pain and were limited. There was a firm non-tender bony mass over the right clavicle. Neurological examination was negative for any focal neuro deficit, presence of weakness or sensory deficit. CT scan of the chest showed numerous lytic lesions present in the ribs, the largest one at the sternal end of the right clavicle, with a non-acute displaced pathologic fracture (figures 1 and 2). Further skeletal survey showed numerous lytic lesions in the calvarium (figure 3) and the ribs.

Figure 1.

CT chest (coronal view) without contrast showing clavicle fracture on the right.

Figure 2.

CT chest without contrast (sagittal view); showing the pathological fracture on the right clavicle.

Figure 3.

CT brain without contrast (axial view); showing numerous lytic lesion in the calvarium.

At the time of admission, white cell count was 8.1×10⁹/L, haemoglobin of 94 g/L (normal range: 135–175 g/L). The basic metabolic panel showed creatinine of 4.630 mg/dL (normal range: 0.6–1.2 mg/dL), blood urea nitrogen of 41 mg/dL (normal 7–20 mg/dL). Proinflammatory marker C-reactive protein (CRP) was elevated at 25 mg/dL (normal < 3 mg/dL). Calcium corrected for albumin was 9.6 mg/dL (normal 8.5–10.5 mg/dL). Serum albumin was low at 3.3 gm/dL, urine total protein was 6275 mg/24 hours (normal < 80 mg). Urine protein electrophoresis was done and showed an M spike of 85.3% and M protein 5352.3 mg/24 hours. The urine light chain qualitative assay was positive for myeloma protein. Serum protein electrophoresis revealed M spike in the gamma region 0.6 g/dL. Further quantification showed IgG level to be 1315 mg/dL, IgA 129 mg/dL and IgM 30 mg/dL. Free light chain assay showed free kappa light chain of 30 019.13 mg/dL, a free lambda light chain of 45.9 mg/dL and a kappa–lambda ratio of 654.4:1 (normal kappa:lambda ratio is 0.26–1.65:1). Bone marrow aspiration showed 80% of plasma cells. Diagnosis of kappa light chain myeloma was made. Fluorescence in situ hybridisation studies confirmed the presence of monosomy 13. Serum beta2 microglobulin was 9.1 mg/dL (normal 1.1–2.4 mg/dL). Laboratory and clinical findings corresponded to MM stage III (criteria by the Revised International Staging System with a median prognosis of 43 months (per the classification).

The multidisciplinary team decided on a management plan, and the patient was started on treatment with bortezomib 1.3 mg/m² of days 1, 4, 8 and 11 along with dexamethasone 40 mg of day 1 through 4, day 8 and day 15. A two-drug regimen was preferred over a three-drug one to avoid toxicity-related adverse effects in the setting of acute renal failure (eg, worsening neutropenia with lenalidomide). The patient is receiving chemotherapy as an outpatient in our hospital and has shown a good response to treatment. His renal function has also improved.

Investigations

CT chest/abdomen, Complete Blood Count (CBC), urinalysis, Serum Protein Electrophoresis (SPEP), Urine Protein Electrophoresis (UPEP), bone marrow aspirate/biopsy.

Differential diagnosis

Benign conditions presenting as chronic shoulder pain include biceps tendinitis, rotator cuff tear, adhesive capsulitis. Polymyalgia rheumatica, as well as brachial neuritis, can present with the same distribution of the pain and symptoms.

Treatment

The patient was initiated on a combination regimen of bortezomib and dexamethasone. Currently, he is undergoing treatment at our outpatient facility.

Outcome and follow-up

The patient continued follow-up with the hematology–oncology team and currently receiving chemotherapy.

Discussion

MM is defined as a clonal proliferation of terminally differentiated plasma cells within the bone marrow and represents an estimated 1.8% of all new malignancies and 18% of all hematologic malignancies in the USA. The patient presents with weakness due to anaemia, backache, bone pain, with or without a pathological fracture.³

There are various ways MM may present: anaemia, generalised malaise, recurrent infection secondary to bone marrow infiltration. Bone pain due to myeloma involvement, pathological fractures and renal failure are common. Less common presentations include those with symptomatic hypercalcemia, hyperviscosity syndromes, coagulopathies, spinal cord compressions and amyloidosis. In approximately one-third of cases, however, the patient remains asymptomatic and diagnosed following a routine laboratory workup.¹

Bone pain in MM is the second most common presentation after anaemia. However, shoulder pain is not common. Solitary plasmacytomas presenting with clavicular fractures have been previously reported in the literature and are extremely rare.⁴

Rarely MM can present with polymyalgia rheumatica-like symptoms with limitations in hip and shoulder movements.⁵ Cerrahoglu et al described a case of MM presenting as shoulder pain with idiopathic brachial neuritis.⁶ Justin Arockiaraj et al described a 65-year-old woman presenting with a chronic, painless bilateral clavicular swelling for 18 months. Plain radiographs revealed expansile osteolytic lesions involving the medial two-thirds of both the clavicles without evidence of pathologic fracture or periosteal reaction. The patient was diagnosed as MM.⁷ Another case report mentioned a young woman presenting with right-sided shoulder pain, later found to be secondary to clavicular fracture and was eventually diagnosed as MM.⁸

In the article by Ong et al, there was a high percentage of patients presenting without apparent symptoms of myeloma but were later diagnosed to have stage III myeloma (as in our case).⁹ Bone involvement in MM has been related to the severity of the disease and adverse outcomes.¹⁰ MMs with fractures have at least a 20% increase in the risk of death compared with patients without pathological fractures.^{10 11}

Skeletal involvement in MM can include discrete lytic lesions called solitary plasmacytomas, generalised skeletal lytic lesions and widespread osteopenia/osteoporosis.¹² Commonly involved sites include the spine, skull and long bones. Lytic deposits are generally visible when a substantial amount of trabecular bone is lost.¹³ There is increased osteoclastogenesis and reduced osteoblastic activity leading to the lesions of MBD. Bone pain, pathological fractures (eg, vertebral body collapse), is the frequent cause of morbidity and mortality in MM.¹⁴

MMs are often seen to not respond to conventional chemotherapeutic agents, particularly the cell-cycle-dependent cytotoxic agents, as the clonal plasma cells are terminally differentiated.¹⁵

Immunomodulatory drugs (ie, thalidomide, lenalidomide and pomalidomide) and the proteasome inhibitors (ie, bortezomib, carfilzomib and ixazomib) have revolutionised the management of newly diagnosed MM. Improved outcomes have led to their widespread incorporation into frontline regimens in both transplant eligible and ineligible patients.^16–18

MM is not commonly encountered in emergency practice; earlier identification of relatively subtle symptoms can help early diagnosis and treatment. Misdiagnosis delays treatment and portends a poor prognosis.

Learning points.

• Multiple myelomas may present with shoulder pain and clavicular involvement.

• The low index of suspicion for myeloma is important as early detection can result in effective treatment and better survival.

• Uncommon symptoms have been linked to advanced stage myeloma with a reduced life expectancy.