An unusual presentation of multiple myeloma

Abstract

The authors report a case of a 58-year-old woman, ex-smoker, who was referred to the respiratory clinic with a presumed unresolving airspace shadowing in the right lung. Further evaluation of the shadowing with a CT thorax revealed rib lesions, a pancreatic lesion and multiple liver lesions, making the diagnosis of metastatic pancreatic carcinoma most likely. However, further blood investigations and imaging eventually revealed the cause for the shadowing to be multiple myeloma, since the unresolving shadowing was actually a rib lesion.

Background

Multiple myeloma (MM) is a clonal proliferation of malignant plasma cells producing a monoclonal immunoglobulin. This case was an unusual presentation of MM, picked up on an initial chest X-ray done for what was thought to be an unresolving air space shadowing, which in retrospect turned out to be a rib lesion secondary to MM.

Case presentation

A 58-year-old Caucasian woman of Maltese origin, ex-smoker, was referred to the respiratory clinic with an unresolving right upper lung zone airspace shadowing on chest X-ray as illustrated in figure 1. The patient had been treated for a lower respiratory tract infection with antimicrobials by her general practitioner. Our main concern at that point was to exclude a primary lung tumour.

Figure 1.

A chest radiograph showing airspace shadowing in the right upper lung zone marked with a white arrow. The inset shows a zoomed image of this air space shadowing.

The patient was clinically well. She denied any cough or sputum, including haemoptysis, or any febrile episodes. She denied weight loss or any loss of appetite. Her only concern was non-specific aches and pains, including back pain, which she attributed to her job, which involved caring for elderly people, including heavy lifting. She had no family history of malignancy. At that point, further investigations including blood investigations and a CT scan of the thorax were ordered. All blood investigations, including a white cell count, inflammatory markers, renal function, liver function and serum calcium levels, were within normal limits.

CT thorax revealed rib lesions, a pancreatic lesion and multiple liver lesions. Figure 2 shows the rib lesion which was thought to be the air space shadowing shown on the previous chest X-ray.

Figure 2.

CT thorax in mediastinal window setting showing a right-sided rib lesion.

Our preliminary diagnosis at this point was metastatic malignancy, possibly with a pancreatic primary.

This was evaluated further with an MR pancreas which revealed liver haemangiomas, an intraductal papillary mucinous neoplasm (IPMN) and multiple bone lesions, involving the ribs, the pelvic bones, and the thoracic and lumbar vertebrae. At this point, both a primary lung tumour and metastatic pancreatic malignancy were excluded, and our suspicion was that of metastatic bone disease with an unknown primary.

Further blood investigations were taken including tumour markers and serum protein electrophoresis. The tumour markers were all within normal limits, however, the serum protein electrophoresis revealed a monoclonal band with IgG predominance. The serum IgG level was raised at 35.5 g/L (normal values: 7–16 g/L). Hence, the diagnosis of MM was highly suspected. The patient was referred to the haematologists and a bone marrow trephine biopsy was performed showing an increase in plasma cells compatible with MM.

A positron emission tomography (PET) scan followed which showed abnormal uptake in multiple vertebrae, several ribs, with the largest uptake in the right third rib, scapulae, humeri, clavicle, sternum, iliac bones and femora.

Outcome and follow-up

The patient is currently being followed up by the haematologists and is being treated with chemotherapy. The chemotherapy regimen being used is a combination of cyclophosphamide, thalidomide and dexamethasone.

In our patient, an IPMN of the pancreas was also detected on imaging. Hence, in view of the risk of malignant transformation, she is also being followed up by the gastroenterologists with annual imaging.

Discussion

MM is a clonal proliferation of malignant plasma cells producing a monoclonal immunoglobulin.¹

The most common clinical manifestations of MM, which indicate organ damage, are known as the CRAB features, an acronym which includes elevated serum Calcium, Renal function impairment, Anaemia and/or Bone involvement.² Less common features include neurological disease and increased risk of infection. In our patient, only bone involvement was present.¹

The revised International Myeloma Working Group (IMWG) criteria include the classic CRAB features and three myeloma defining events (MDEs). The presence of at least one MDE is sufficient for a diagnosis of MM, even in the absence of CRAB features.

The new IMWG definition of active MM is clonal bone marrow plasma cells >10% or biopsy-proven bony or extramedullary plasmacytoma and any one or more of the CRAB features (mentioned above) or one or more of the following MDEs, which are biomarkers of malignancy:

• 60% or greater clonal plasma cells on bone marrow examination.

• Serum involved/uninvolved free light chain ratio of 100 or greater, provided the absolute level of the involved light chain is at least 100 mg/L.

• More than one focal lesion on MRI that is at least 5 mm or greater in size.³

MM should be distinguished from other plasma cell proliferative disorders, most commonly monoclonal gammopathy of undetermined significance (MGUS), smouldering MM (SMM) and solitary plasmacytoma. This distinction is important as progression to MM, treatment and prognosis will be different.^{4 5}

The presence of bone involvement in MM is the main cause of morbidity. Around 60% of patients with MM have lytic bone lesions present at diagnosis.¹ Although our patient did have multiple aches and pains, including back pain, she attributed it to strenuous activity during her job as a carer. The fact that she was over 50 years of age, was a red flag. A thorough history and examination cannot be overemphasised when dealing with back pain.

Red flags for back pain include a history of cancer, older than 50 years, unexplained weight loss, long duration of pain especially if present for more than 1 month, nocturnal pain and unresponsiveness to analgesia.⁶

After a thorough history and examination, MM testing includes blood and urine investigations, namely a complete blood count with differential and peripheral blood smear, renal function, serum calcium, serum protein electrophoresis, immunoglobulin levels, urinalysis, 24-hour urine collection for proteinuria, electrophoresis and immunofixation.³

Ninety-seven per cent of patients with MM will have a monoclonal (M) protein produced and secreted by the malignant plasma cells. The malignant plasma cells can produce both immunoglobulin heavy chains and light chains, light chains alone or neither, with IgG being the the most common heavy chain produced, being found in 50% of cases. In most cases, kappa is the predominant light chain compared with lambda, by a factor of 2 to 1. In our patient, a paraprotein IgG kappa was isolated on serum protein electrophoresis.^{1 7}

After the above investigations, if the diagnosis of MM is still highly suspected, a bone marrow aspirate and biopsy are key to the diagnosis of MM. The bone marrow of the majority of patients with MM will contain 10% or more clonal plasma cells.¹

Imaging is crucial for the assessment of patients with suspected MM. Cross-sectional imaging is preferred because these modalities are more sensitive than plain radiographs for the detection of skeletal lesions in myeloma. For patients with suspected MM, IMWG suggest a low-dose whole body CT (LDWBCT) as a baseline assessment of bone involvement. For patients with suspected extramedullary disease outside of the spine, a whole body PET/CT is recommended.³

Evidence of one or more sites of osteolytic bone lesions on CT (including LDWBCT) or PET-CT satisfies the criteria for bone involvement in MM, regardless of their presence or absence on plain radiography.³

The differential diagnosis of MM includes other plasma cell proliferative disorders mentioned above such as MGUS, SMM, solitary plasmacytoma or primary amyloidosis, and other diagnoses such as lymphoma, chronic lymphocytic leukaemia, bone malignancy and metastatic carcinoma.⁸

Since MM may present with multiple symptoms, diagnosis is challenging, hence a high index of clinical suspicion is vital. It may present in ample ways, usually either with symptoms related to the CRAB features, mostly back pain, or an infectious process or secondary to a pathological fracture.

Pulmonary and pleural involvement by MM has been documented in various instances. The most common thoracic involvement by MM is bone involvement or presence of a lung infiltrate secondary to an infectious process.⁹ MM involvement can be intramedullary or extramedullary. In our patient, lung involvement was intramedullary as what was thought to be a non-resolving lung lesion turned out to be a rib affected by MM.

A comparative analysis of pulmonary presentations in MM by various authors revealed the following: mass lesion (hilar or intraparenchymal), pulmonary calcification, multiple lung nodules, pneumonia, pleural involvement and rib erosion.⁸ A review of 958 patients with MM, published in 1978, revealed that thoracic skeletal or pleuropulmonary involvement or both were present in 46% (443) of patients. The most frequent finding, exclusive of plasmacytomas, was thoracic skeletal abnormality, with osteolytic lesions being the the most common.¹⁰

The lung parenchyma is an infrequent site of extramedullary involvement in MM. In a case report published in 2014, MM was diagnosed at bronchoscopy as monoclonal plasma cells were established from bronchoalveolar lavage samples.¹¹ In another case report published in the Journal of Clinical Oncology, MM presented as interstitial lung disease.¹²

Kushwaha et al demonstrated a case in which MM mimicked bronchogenic carcinoma, as imaging showed a left upper lobe mass and a left pleural effusion, however, biopsy of the lung mass revealed atypical plasma cells.¹³ The latter is similar to our case in that MM mimicked lung cancer radiologically. However, it differs from our case, as the lung mass reported in the case by Kushwaha et al turned out to be an extramedullary plasmacytoma. In our case what was thought to be a lung lesion turned out to be a rib affected by MM, that is, intramedullary MM.

Due to the multiple modes of presentation of MM, the physician should have a high index of clinical suspicion and should take MM into consideration in the differential diagnosis of pulmonary and pleural infiltration.

Learning points.

• One should not assume that an opacity on a chest X-ray is always due to a lung lesion.

• When investigating back pain, one should start with a thorough history to exclude red flags.

• In tricky cases of an unknown primary, the physician should keep an open mind, and think of the possibility of plasma cell proliferative disorders, such as multiple myeloma.

• Multiple myeloma may have different presentations and the diagnosis can be challenging, hence it should be taken into consideration in the differential diagnosis of pulmonary and pleural infiltration.