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Putrescence to Quintessence: An Atypical Presentation of Multiple Osteoporotic Spinal Fractures Masquerading as Multiple Myeloma

A 64-year-old male patient presented with multiple osteoporotic spinal fractures of unknown origin. He was provisionally diagnosed with multiple myeloma based on biochemical and radiological findings. The patient presented in a very frail condition with a questionable outcome but showed a remarkable recovery from being frail to relatively fit. His baseline characteristics including magnetic resonance imaging of the dorsolumbar spine, beta 2 microglobulins, and C-reactive protein improved. The diagnosis was later changed to multiple spinal osteoporotic fractures. In this case report, we highlight that, although it is a good practice to have a single working diagnosis, when the diagnosis is challenging, a holistic approach should be followed to prevent medical and diagnostic miscalculations.


Introduction
Multiple myeloma (MM) presents with varied phenotypes, and multiple spinal osteoporotic fractures with constitutional symptoms suggest malignancy [1]. Apparent immunoglobulin (Ig)G, IgA, IgM, and IgE aberrations in serum electrophoresis, along with the presence of light and heavy chains, suggest the diagnosis of MM [2,3]. Although the prevalence of kappa and lambda light chains [4,5] or any of the other types of heavy chains is not uncommon, an insidious case presenting with multiple spinal fractures and very high beta-2 microglobulin (β2M) levels with classical clinical features warrants a diagnosis of myeloma. In most phenotypes of MM, plasma cells proliferate with a neoplastic propensity, producing a monoclonal Ig [6]. This plasma cell type is pathognomonic for bone metastasis, causing widespread skeletal damage, osteoporosis, osteopenia, and compression spinal collapse or fracture.
In addition to monoclonal Ig aberration, another important factor in MM pathobiology is increased β2M levels [7]. In humans without any known genetic variation, β2M is present unequivocally in almost all cells and fluids such as the serum, urine, and cerebrospinal fluid (CSF). There are at least two different ways by which β2M is mechanistically involved in the pathogenesis of MM. It is also related to frailty concerning general and skeletal health in individuals over the age of 60 [8].
Structurally, β2M has seven β-strands organized into two β-sheets linked by a single disulfide bridge, presenting a classical β-sandwich resembling Ig. β2M has a distinctive molecular structure, constant-1 Ig superfamily domain, and immune molecule complexes such as major histocompatibility complex (MHC) class I and II [9]. β2M consists of two molecularly unique tryptophan (Trp) residues that play differential and complementary roles in its structure, guiding it towards the spontaneous and suicidal aggregation into amyloid fibrils [10,11]. Along with interleukin-1β (IL-1β), it shows involvement in bone-related conditions, promoting a cell-mediated calcium efflux causing osteoclast stimulation and osteoblast-osteoclast disbalance favoring lytic destruction and bony metastasis [12]. In this case, the diagnosis became complex and led to a clinical dilemma when a 64-year-old male patient initially presented with clinical, biochemical, radiological, and histopathological features consistent with MM but rapidly recovered and contrasted the previous findings within five months. Informed consent was taken from the patient before preparing this manuscript.

Case Presentation
A 64-year-old, diabetic, non-smoker male patient presented to the emergency department with an acute episode of severe lower back pain, inability to walk, and being completely bedridden. He also complained of difficulty in urination for three days. The patient had generalized swelling with pitting edema in both lower limbs. He was a known patient of type two diabetes mellitus for more than 25 years and was on oral hypoglycemic drugs and insulin. There was no history of trauma or similar episodes of illness, and there was no significant family history. This case discussion is based upon two rounds of workup conducted between March and August 2019. The discussion encompasses the chronological events related to investigations, differential and provisional diagnoses, management plans, treatment, recovery, and follow-up.

Laboratory analysis
In March 2019, after the first presentation with acute back pain, magnetic resonance imaging (MRI) of the dorsolumbar spine revealed the partial collapse of D5, D6, D10, D12, L1, and L4 vertebrae and the irregularity of endplate with marrow edema. A diffuse disc bulge indenting the anterior thecal sac was noted at the L1-2, L3-4, L4-5, and L5-S1 levels along with bilateral neural foramina compression. Facet joint arthropathy with ligamentum flavum hypertrophy was recorded at multiple levels in the lumbar spine. Screening of the entire spine revealed loss of cervical lordosis with osteophytes and disc desiccation changes at various levels. MRI findings of the spine strongly suggested malignancy ( Figures 1A, 1B). The overall spine health was poor, further evidenced by a bone mineral density (BMD) scan with a T-score of -3.5 and a Z-score of -3.1 ( Table 1). Whole-body positron emission tomography-computed tomography (PET-CT) images (vertex to mid-thigh) were acquired in the three-dimensional mode. Findings suggested mildly hypermetabolic cervical, axillary, and abdominal lymph nodes, likely inflammatory with partial collapse of multiple vertebrae ( Figure 1C). Digital X-rays of the skull, both lateral and frontal view, did not show any abnormality, and there were no signs of punched-out lesions ( Figures 1D, 1E).    Hematopoietic cells showed all three lineages. There was no evidence of granuloma, atypical, or malignant cells in multiple serial sections; however, this was not entirely conclusive against malignant signatures ( Figure 2, Panels A, B). Basic biochemistry, routine, and microscopic urine examination were performed. Postprandial blood glucose and C-reactive protein (CRP) were elevated. Moreover, urine microscopy revealed an increased white blood cell (WBC) count ( Table 1).
Standard testing protocols were performed including serum protein electrophoresis, immunotyping, free kappa and lambda light chains (serum and urine) [13]. Serum β2M level was markedly elevated along with elevation of light chains, both in serum and urine (    Table 1). MRI of the dorsolumbar spine, serum protein electrophoresis, gel fixation ( Figure 2, Panel D), immunofixation, light chain estimation (serum and urine), immunotyping, and β2M estimation were repeated ( Table 2).

Differential diagnosis and treatment
Based upon the clinical features and laboratory findings, we considered multiple myeloma, tuberculosis of the spine, metastatic prostate carcinoma, lymphoplasmacytoid lymphoma, disuse osteoporosis, and isolated β2M-associated osteoporotic compression fracture. The patient was given symptomatic treatment when he first presented in March 2019. Initially, baseline correction was done for electrolytes, blood glucose, and other constitutional symptoms. The patient was on disease-modifying drugs such as ibandronate, calcium, and vitamin D supplements. Physiotherapy for flexibility, spinal range of motion, and strengthening exercises were advised. The patient was followed up in August 2019. On follow-up, his physical condition had improved, and he could walk and perform daily activities without support. Moreover, his pain was entirely resolved.

Discussion
This is a typical case that addresses the dilemma raised in scenarios of unclear diagnosis and tentative treatment plans. When this patient first presented in March 2019, his physical and clinical findings were suggestive of a diagnosis of MM. Numerous spinal fractures, poor bone density, clinical symptoms, a very high level of β2M, and unclear histopathological findings led us to consider malignancy and plan appropriate treatment. Even when we weighed the second option of excluding myeloma, the vertebrae health was very fragile; hence, we planned for bone cementing between L1-4 to preserve the long-term mobility and the general health of the patient. However, the absence of malignant cells in core needle vertebral biopsy, no relevant findings on PET-CT scan, no lytic lesion on the skull, lack of M-band in electrophoresis, and no malignancy-related anomalies on immunofixation and immunotyping compelled us to think otherwise. We ruled out prostate cancer based on prostate-specific antigen levels along with Gleason's score of less <7 on a digital rectal examination [14]. Tuberculosis of the spine was ruled out based on the clinical, biochemical, microbiological, and radiological findings. Secondary metastasis and lymphoplasmacytoid lymphoma were ruled out because of the absence of any metastasis and blood findings. Disuse osteoporosis is a subjective diagnosis and can exist along with any of the differential diagnoses mentioned earlier. After five months, when the patient presented for a follow-up, his recovery was remarkable. On follow-up, he walked without support to the outpatient department. MRI of the spine showed improvement, BMD showed improved density, and CRP along with most of his important biochemistry markers had reached the baseline. Most remarkably, the β2M, serum and urinary proteins, and kappa and lambda light-chain (serum and urine) levels were within the normal range (Tables 1, 2).
The differential diagnoses were ruled out based on the above observations and findings, and a final diagnosis of multiple spinal osteoporotic fractures was made.

Learning points
According to the doctrine of Occam, multiple entities should not be considered without necessity. In this context, it is always better to consider a single working diagnosis and follow a single treatment plan, even for complex diseases [15]. However, at the same time, confirming a diagnosis can be challenging. Other than MM, the differential diagnoses include secondary metastasis from an occult primary, lymphoma, and infections such as tuberculosis [16]. We constantly reviewed the patient, with the view to make a specific diagnosis, we were concerned because of the uncertain diagnosis. Although osteoporotic fracture, MM, and elevated β2M are not uncommon, together they can raise clinical confusion in a frail patient.

Conclusions
Our patient thought that he might not walk again in his life. We weighed all the options for interventions. Additionally, we assessed his condition with careful and critical analysis, performed all the necessary investigations, excluded MM, and opted for non-surgical conservative management. The treatment plan led to the remarkable recovery of the patient.

Additional Information Disclosures
Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.