Persistent Rib and Thoracic Pain: A Non-Secretory Multiple Myeloma Case Study

This non-secretory multiple myeloma case study follows the assessment and investigation of a 72-year-old woman who presented with persistent rib and thoracic spine pain.

The case demonstrates the importance of clinical reasoning, objective assessment and being prepared to reconsider an initial diagnosis when a patient's symptoms do not progress as expected.

The patient's initial investigations appeared consistent with osteoporosis and a thoracic vertebral compression fracture. However, persistent rib pain and significant focal bony tenderness prompted further investigation, ultimately leading to a diagnosis of non-secretory malignant myeloma.

Clinical case study: Patient information has been anonymised. This resource is provided for educational purposes and should not be used to diagnose or manage an individual medical condition.

Initial referral and presentation

The patient, referred to here as CS, was a 72-year-old woman triaged to an Advanced Musculoskeletal Practitioner spinal clinic.

The original referral described pain affecting the left chest wall for approximately 10 to 12 weeks. A topical non-steroidal anti-inflammatory drug had appeared to help temporarily, but the symptoms had returned and she had subsequently developed thoracic spine pain.

Localised tenderness had previously been identified around one of the ribs and a chest X-ray had been requested, but this investigation had not gone ahead.

Because the assessment took place during the COVID-19 pandemic, the initial consultation was conducted by telephone.

Description of the pain

CS described bilateral rib pain alongside central thoracic spine pain, although she felt the right-sided symptoms were slightly worse than the left.

She described the pain as being specifically "in her ribs".

The symptoms did not radiate further forwards than approximately the line of the axilla. The pain was constant but could move between the right and left sides.

She described:

• A constant dull, aching pain

• Intermittent sharper catches of pain

• Pain aggravated by deep breathing

• Pain aggravated by coughing

• Pain aggravated by general activity

• Difficulty getting comfortable

• A tendency to move more slowly and carefully because of the symptoms

She felt more comfortable when lying on a firm mattress.

TENS and topical Voltarol gel provided some relief.

There were no reported pins and needles, tingling or numbness, and no proximal or distal referral of symptoms.

CS also denied:

• Bladder or bowel symptoms

• Saddle anaesthesia

• Alteration to gait control

• Unexplained weight loss

• Sleep disturbance

• Any particular diurnal pattern to the pain

How the symptoms developed

The symptoms had started approximately six weeks before the initial assessment.

At the time, CS had been gardening and moving heavy plant pots. She could not recall a particular incident involving sudden or sharp pain and did not experience a clear click or pop while moving them.

Approximately two days later, however, she noticed a slight popping sensation underneath the left side of her rib cage.

The following morning she woke with severe left-sided pain, predominantly around the front of the ribs. This then quickly progressed posteriorly towards the thoracic spine.

The pain was considerable.

CS contacted her GP, who examined her to exclude shingles. Analgesia was prescribed, although there were limitations on what she could tolerate because of existing stomach and bowel problems.

Approximately two weeks before the Advanced Musculoskeletal Practitioner assessment, the pain had become severe enough for CS to call an ambulance.

She described a "band of pain" extending from the thoracic spine around the ribs.

No investigations were completed in A&E. Further analgesia was provided and she was advised to return if the symptoms did not resolve.

By the time of the initial assessment, the overall intensity had eased slightly.

Previous history and initial investigations

CS had not experienced thoracic spine pain like this previously.

She reported some previous lower back pain, but nothing comparable to her current symptoms.

Her GP had previously requested a chest X-ray, but this had been declined because CS was not reporting shortness of breath.

A number of blood tests had also been arranged, including:

• Urea and electrolytes

• Calcium and albumin

• Thyroid function tests

• Full blood count

• Magnesium

• Vitamin B12

• Alkaline phosphatase

These had been reported as normal.

Medically, CS was otherwise relatively fit and well.

She had a longstanding history of irritable bowel syndrome and diverticulitis, although this was stable.

She also had a vitamin B12 deficiency and received regular injections.

Her medication included paracetamol, lansoprazole and bendroflumethiazide.

Importantly, a previous hip X-ray from 2019 had reported diffuse osteopenia.

Initial clinical reasoning

Based on the history and information available at this point, the provisional diagnosis was a possible thoracic spine wedge fracture secondary to previously undiagnosed osteoporosis.

The rib pain could potentially have represented referred pain from the thoracic spine or additional osteoporotic rib fractures.

There were some reassuring features.

Recent blood tests had been relatively normal, although immunoglobulins and protein electrophoresis had not been included.

There was:

• No night waking

• Some relief when lying supine

• No bladder or bowel disturbance suggesting spinal cord compression

• No unexplained weight loss

However, the presentation remained slightly unusual.

In particular, there had been a delay between moving the heavy pots and the onset of significant pain, which differed somewhat from previous thoracic wedge fractures encountered clinically.

Given that the previous chest X-ray had not been undertaken, a plain X-ray of the thoracic spine was arranged.

Further blood investigations were not requested immediately because the GP had recently completed a number of blood tests. The decision was made to await the thoracic X-ray findings first.

Thoracic spine X-ray findings

The thoracic spine X-ray reported:

• A severe wedge compression fracture of T8

• Increased thoracic kyphosis

• Mild multilevel spondylotic disease throughout the thoracic spine

• Narrowing of the upper to mid-thoracic intervertebral disc spaces consistent with degenerative disc disease

• Markedly demineralised skeletal appearances

Following these findings, a FRAX score was calculated.

The scores were:

• Major osteoporotic fracture: 22

• Hip fracture: 7

An attempt was made to arrange a DEXA scan directly, but the request was declined because of referral rights.

CS's GP was therefore contacted and asked to arrange the investigation.

Additional blood tests were also undertaken.

Further blood investigations

The additional blood results included:

Test	Result
Adjusted calcium	2.7 mmol/L
Protein	59 g/L
Globulin	11 g/L
IgA	0.27 g/L
IgG	3.39 g/L
IgM	0.12 g/L

Other investigations, including paraproteins, were reported as showing no abnormality of note.

The adjusted calcium was slightly above the stated reference range of 2.2 to 2.6 mmol/L.

Protein, globulin and immunoglobulin levels were below their stated reference ranges.

DEXA scan and osteoporosis diagnosis

The DEXA scan subsequently reported:

Lumbar spine, L1 and L3

• T-score: -3.6

• Z-score: -1.5

L2 was excluded because of artefact and L4 because degenerative change made the measurement unreliable.

Left femoral neck

• T-score: -2.6

• Z-score: -0.7

• Bone mineral density: 0.555 g/cm²

Total left hip

• T-score: -2.2

• Z-score: -0.5

Using the World Health Organisation classification, the patient was classified as osteoporotic.

At this stage, there appeared to be a clinically reasonable explanation for the T8 fracture and much of the presentation.

When the clinical picture stopped fitting

Once all the results were available, CS was contacted and the findings were explained.

The diagnosis appeared consistent with osteoporosis. However, during that conversation an important discrepancy emerged.

The thoracic spine pain had begun to ease.

The rib pain had not.

CS reported that the rib pain remained as severe as ever and clearly expressed her concern.

This was significant because the working clinical hypothesis had been that the rib pain was referred from the thoracic spine.

If the thoracic spine pain was improving while the rib pain remained severe, that explanation no longer fitted the patient's progress particularly well.

A face-to-face assessment was therefore arranged.

Face-to-face clinical examination

On examination, CS presented with mild thoracic kyphosis but no scoliosis.

Thoracic spine movement was well preserved in all directions.

There was only minimal tenderness over the spinous processes around T7 to T9.

The findings on examination of the ribs were much more concerning.

The contour of the ribs felt unusual on palpation and there was exquisite focal bony tenderness along several rib shafts.

A chest X-ray was therefore arranged.

Chest X-ray findings

The chest X-ray identified bilateral destructive bone lesions involving several ribs.

The report described lesions affecting the left lateral and anterior fifth ribs and the right posterolateral fifth and sixth ribs.

A left basal pleural effusion was also noted.

No obvious pulmonary mass was identified.

The radiology report recommended CT imaging of the chest, abdomen and pelvis to investigate for a potential primary malignancy, alongside appropriate biochemical tests.

In line with the clinical pathway, acute oncology services were contacted because of the possibility of metastatic disease with an unknown primary.

CS's care was subsequently transferred to acute oncology services.

CT investigation

CT imaging of the thorax, abdomen and pelvis demonstrated multiple expanding lytic and soft tissue lesions affecting the ribs bilaterally.

There were also innumerable lytic lesions throughout the imaged skeleton.

The T8 vertebra was described as vertebra plana.

There was no supraclavicular, axillary, mediastinal or hilar lymphadenopathy and no pulmonary mass or nodule was identified.

Some pleural thickening was seen at the left lung base, accompanied by linear atelectatic change.

No pulmonary consolidation was seen and the main airways remained patent.

The scan also reported:

• No central pulmonary artery embolus

• Multiple benign-appearing liver cysts

• No biliary dilatation

• Normal appearances of the spleen, pancreas, adrenal glands and kidneys

• No free fluid or lymphadenopathy within the abdomen or pelvis

• No significant abnormality of the unprepared small or large bowel

The conclusion described diffuse lytic skeletal lesions with multiple expanding soft tissue rib lesions bilaterally.

The differential diagnosis included multiple myeloma or secondary lesions from an unknown primary malignancy.

Discussion at a haematology multidisciplinary team meeting was advised.

An addendum agreed that the findings were suggestive of either myeloma or metastases from an unknown primary.

There was also early soft tissue encroachment towards the spinal canal at T8 due to posterior cortical expansion, with consideration recommended as to whether urgent MRI investigation was required.

Further imaging and investigation

The patient's imaging was reviewed by the acute oncology and unknown primary multidisciplinary team.

Further nuclear medicine imaging identified a 23 mm lytic lesion within the left scapula with mild peripheral FDG activity.

Other findings included:

• Further areas of mild FDG activity in the left scapula

• Several additional lytic lesions without significant FDG activity

• Multiple bilateral rib lesions

• Low-grade FDG activity in some rib lesions

• Soft tissue plasmacytomas affecting the left lateral sixth rib and right posterolateral fifth rib

• A soft tissue nodule in the upper back with low-grade activity

• Mild FDG activity within the inferior sternum

• T8 vertebral wedge collapse

• Probable partial collapse of the adjacent T7 and T9 vertebral bodies

• Multiple lytic lesions within the spine and pelvis

• Heterogeneous bone marrow activity suspicious for disease involvement

• Moderate bilateral pleural effusions

The overall impression was widespread lytic bony disease compatible with known myeloma, with varying levels of FDG activity.

Subsequent laboratory investigations

Further investigations included repeat electrophoresis and Bence Jones testing.

Bence Jones testing showed no abnormality of note.

Repeated electrophoresis again did not demonstrate the expected abnormal protein spike.

However, serum free light-chain testing produced the following results:

• Free Kappa: 42.0 mg/L

• Free Lambda: 5.4 mg/L

• Kappa ratio: 7.78

The patient was ultimately diagnosed with non-secretory malignant myeloma (NSMM).

Understanding non-secretory malignant myeloma

Malignant myeloma is a plasma cell disorder characterised by the presence of clonal plasma cells within the bone marrow.

These malignant plasma cells usually secrete an abnormal immunoglobulin, creating a monoclonal gammopathy.

The abnormal protein, commonly referred to as monoclonal protein or M-protein, can generally be detected within serum or urine using electrophoresis.

The disease can cause end-organ damage and patients may present with manifestations involving:

• The blood, including anaemia and hypercalcaemia

• The kidneys, including renal failure

• The skeleton, including lytic bone lesions

Non-secretory malignant myeloma has essentially the same clinical and radiological features as malignant myeloma.

The important difference is that, in NSMM, secretion of the immunoglobulin may be impaired or absent.

As a result, serum and urine electrophoresis can appear normal.

Different subgroups of NSMM

The literature cited within this case study describes four potential subgroups.

1. Free light-chain myelomas or oligo-secretors

There is impaired immunoglobulin production and small amounts of free light chains are secreted.

These may not be detected using serum electrophoresis but can be identified with a serum free light-chain assay.

This appeared to be the situation in this patient's case.

2. Non-producers

There is a complete absence of immunoglobulin production, resulting in no secretion and no measurable protein within the blood or urine.

Within the classification discussed in the source literature, "true" NSMM should only refer to this group.

3. True non-secretors

The myeloma cells produce immunoglobulin molecules but are unable to secrete them.

4. False non-secretors

These are myeloma variants or related plasma cell diseases where measurable intracellular immunoglobulins are present but standard testing does not demonstrate extracellular components, despite pathological evidence of secretion.

How rare is non-secretory malignant myeloma?

The literature reviewed within the original case study reported that malignant myeloma accounts for approximately 1% of malignant disease and around 13% of haematological malignancies.

Non-secretory malignant myeloma was reported to represent approximately 3% to 5% of malignant myeloma cases.

When only "true" non-secretory myeloma is considered, the estimated incidence falls to approximately 1% to 2% of all malignant myeloma cases.

The literature also describes NSMM presenting through recurrent vertebral compression fractures and suggests that it should be considered as a differential diagnosis when multiple or recurrent vertebral fractures occur despite an absence of detectable monoclonal immunoglobulins in serum and urine analysis.

Once diagnosed, treatment of NSMM is described as being the same as for malignant myeloma.

Clinical reflections from the case

This was a particularly difficult case because the initial investigations provided a plausible explanation for the patient's symptoms.

The thoracic X-ray demonstrated a significant compression fracture.

The skeleton appeared markedly demineralised.

The DEXA scan confirmed osteoporosis.

It was therefore reasonable initially to believe that the presentation was attributable to osteoporosis and associated fractures.

However, something still did not completely fit.

A particularly important point came when the thoracic spine pain improved but the rib pain did not.

If the rib symptoms were predominantly referred from the thoracic spine fracture, improvement in the spinal symptoms might reasonably have been expected to correspond with improvement in the rib pain.

Instead, the rib pain remained severe.

That discrepancy led to the clinical hypothesis being reconsidered.

The importance of listening to the patient

In retrospect, the patient herself appeared to feel that something was not quite right.

Her concern, combined with the change in the relationship between the thoracic and rib symptoms, contributed to the decision to reassess her face-to-face.

Reviewing the original history also highlighted aspects that were somewhat atypical, including the time delay between moving the heavy plant pots and the eventual onset of the severe symptoms.

The importance of objective examination

The face-to-face examination proved particularly important.

Thoracic spine movement was good and spinal tenderness was minimal.

This contrasted considerably with the findings over the ribs.

Their bony contour felt unusual and the degree of focal tenderness was particularly marked.

The severity of the pain on direct palpation of the ribs became one of the most concerning findings and ultimately directed further investigation.

The case therefore reinforced the value of appropriate objective examination, particularly following the changes to clinical practice that occurred during the COVID-19 pandemic.

It also highlighted the importance of specifically assessing for bony tenderness as part of an appropriate musculoskeletal examination.

Learning from an unusual presentation

NSMM is a rare condition and was not initially the suspected diagnosis in this patient.

The case reinforced the importance of remaining open to less common explanations when the clinical presentation does not behave as expected.

The patient had already spoken with her GP on several occasions.

Blood tests had been undertaken and chest X-rays had previously been requested but had not gone ahead.

Ultimately, it was the eventual chest X-ray that identified the destructive rib lesions and changed the direction of the patient's care.

For the clinician involved, the severity of the pain on palpation of the ribs was the finding that most strongly prompted further investigation.

How this case changed the local myeloma screening pathway

The case was subsequently presented to both MSK physiotherapy and medical colleagues during an Interesting Case Studies in-service training session.

Following the outcome of this case, the pathway used for blood testing when screening for suspected myeloma was changed.

Serum free light chains were subsequently included as part of the standard myeloma screen.

The revised screening pathway included:

Biochemistry

• Urea and electrolytes and eGFR

• Liver function tests

• Glucose, random or fasting where appropriate

• Calcium and albumin

• C-reactive protein

• Thyroid function tests where indicated

Haematology

• Full blood count

• Erythrocyte sedimentation rate

Other tests

• eGFR

• PSA where appropriate

• Immunoglobulins

• Protein electrophoresis

• Serum free light chains

• HbA1c where indicated

Additional tests highlighted in the pathway were to be considered where weight loss was present.

The inclusion of serum free light chains was particularly relevant to this case because standard electrophoresis had not identified the abnormality, whereas free light-chain testing demonstrated the raised Kappa result and abnormal Kappa ratio.

Key learning points

This non-secretory multiple myeloma case study highlights several principles relevant to advanced musculoskeletal assessment:

1. A diagnosis should be reconsidered when the patient's symptoms stop behaving in the way expected.

2. A plausible initial diagnosis does not necessarily explain every symptom.

3. The patient's own concerns and description of their symptoms are an important part of clinical reasoning.

4. Face-to-face objective examination can provide important information that cannot always be obtained through remote assessment.

5. Focal bony tenderness can be an important finding during musculoskeletal examination.

6. Further investigation and onward referral may be appropriate when a clinical presentation does not fit a typical musculoskeletal pattern.

7. Reflecting on unusual clinical cases can lead to changes in future clinical practice.

About Dunham Physio

Dunham Physio is based in Dunham Massey, near Altrincham.

Steph is an Advanced Musculoskeletal Practitioner and First Contact Practitioner with extensive experience assessing musculoskeletal conditions and more complex presentations.

A thorough MSK assessment involves more than simply identifying an area of pain. It requires consideration of the patient's history, symptom behaviour and physical examination findings, alongside recognition of when further investigation or onward medical assessment may be necessary.

If you are experiencing persistent musculoskeletal pain, reduced mobility or symptoms that are affecting your day-to-day activities, you can contact Dunham Physio to arrange an assessment.

References

Corso A and Mangiacavalli S (2017). Non-secretory Myeloma: Ready for a new definition? Mediterranean Journal of Hematology and Infectious Diseases; 9; e2017053.

Maeng YH, Hyum CL, Han SH, Seong GM, Song DH, An HJ and Koh HM (2018). Nonsecretory Multiple Myeloma Presenting as Recurrent Vertebral Compression Fractures in an Older Male Patient. Annals of Geriatric Medicine and Research; 22(2); 98–101.

Uche E, Akinbami A, John-Olabode S, Dosunmu A and Odensanya M (2015). A Rare Case of Nonsecretory Multiple Myeloma in Lagos, Nigeria: A Case Report and Literature Review. Case Reports in Medicine; ID 648069.