Discussion
MM is a hematological malignant neoplasm defined by abnormal
proliferation of B-cell lineage malignant plasma cells in the bone
marrow and the release of a significant number of monoclonal
immunoglobulins [3, 11]. MM accounts for 1% of all cancers and 10%
of all hematologic malignancies. In the United States, about 32,000 new
cases are diagnosed each year, with nearly 13,000 patients dying from
the condition, and the yearly age-adjusted incidence has remained stable
at around four per 100,000 for decades [6]. Geographically,
Australia, Europe, and North America have the greatest incidences of the
disease [3]. Males are more likely than females to develop MM, and
African-Americans are twice as likely as Caucasians to develop the
disease. Patients’ median age at the time of diagnosis is around 65
years old [6]. The marrow-containing bones of the vertebrae, pelvis,
and femur are the most prevalent sites for MM, but lesions can occur in
any bone [3]. The majority of tumor cells are restricted to the bone
marrow. However, malignant plasma cells can break through the bone
marrow and periosteal tissue, creating tumorous masses in the nearby
bone site. Additionally, the cells may enter the bloodstream and invade
the distal tissue to produce tumorous masses known as extramedullary
multiple myeloma (EMM). Extramedullary-bone related (EMB) refers to the
adjacent bone, while extramedullary extraosseous (EME) refers to the
extramedullary plasmacytoma distal to the bone.EMM can be found in the
diagnosis of MM or the recurrence of the disease, with an incidence of
3–30% in the diagnosis and 6–40% in the refractory relapse of the
disease. EMB has an incidence rate of 6-35 percent, while EME has an
incidence rate of 0.5-3.5 percent [11]. In our case, a 41-year-old
male diagnosed with MM in the vertebrae, a spinal cord metastasis was
revealed as a recurrence of the disease. EMM, which occurs outside of
the bone marrow, has a poor prognosis and can rarely infiltrate the
central nervous system (CNS), with about 1–2% of patients with MM
developing a secondary CNS malignancy, resulting in neurologic deficits,
disability, and a lower quality of life. The most common form of CNS EMM
is intracranial metastasis, which is thought to be caused by
hematogenous dissemination or contiguous seeding from local lytic bone
lesions. Intramedullary spinal cord metastases, on the other hand, are
extremely uncommon. In the last 17 years, seven cases with
intramedullary spinal cord MM or plasmacytoma metastasis have been
recorded, including our patient. Six of the patients were males and one
female patient. From the cervical cord to the cauda equina, the level of
spinal cord metastases varied [5]. Although our patient is the first
to present with a metastasis extending from the level of the second
dorsal vertebra (T2) to the entire cauda equina. MM has an etiology that
is unknown. Occupational/environmental risk factors such as asbestos,
petroleum, farming, and ionizing radiation have been confirmed to have
an association with the disease in some studies. MM is caused by
multiple genetic mutations in plasma cells and the immunoglobulins they
produce, although some cases of familial MM, which suggest a hereditary
basis, have been reported. MM tumors can develop spontaneously or as a
result of the pre-malignant condition known as ”monoclonal gammopathy of
unknown significance” (MGUS) [3]. MGUS affects more than 3% of the
population over the age of 50. At a rate of 1% each year, it develops
into MM or related cancer [6]. The mechanisms that lead to the
progression of MGUS to myeloma are uncertain. However, they share gene
translocations that code for both heavy and light chains (IgH and IgL).
Abnormalities on chromosome 13 are also common, occurring in around half
of all cases, and are linked to a worse prognosis [3]. MM has a wide
range of clinical manifestations. The key concerns are referred to as
CRAB (hypercalcemia, renal impairment, anemia, and bone lesions). The
presence of a combination of these symptoms should raise the diagnostic
suspicion of myeloma [12, 13]. However, muscle weakness is the most
common presenting neurologic deficit in patients with spinal cord
metastasis, occurring in five of seven cases reported in the literature,
including our patient, who presented with weakness in the lower
extremities with a ⅖ strength, followed by paresthesia in two of seven
cases, and loss of tendon reflexes in two cases, including our case.
Paresis, paraparesis, tetraparesis, sensory deficit, ataxia, and gait
difficulty are among the other symptoms [5]. Our patient also had
hypotonia and uncontrolled sphincters. This disease’s differential
diagnosis includes MGUS, plasmacytoma, astrocytoma, and lymphoma [5,
13]. The IMWG has devised diagnostic criteria to effectively
distinguish between them and MM [12]. The presence of monoclonal
protein in the serum or urine, with a positive bone marrow biopsy
revealing more than 10% plasma mono-clonal cells and at least 1 finding
for organ failure according to the CRAB acronym, is indicative of MM
[12, 13]. In our case, the bone marrow biopsy showed more than 60%
IGG kappa plasma cell infiltration. After treatment and during the new
onset of symptoms, a second biopsy was performed and displayed less than
5% infiltration and no monoclonal protein peak in the blood smear
electrophoresis, which reflects a state of inactivity of the disease in
the bone marrow (Fig.3). MM affects the bone, especially the axial
skeleton, in up to 90% of patients [7]. Bone lytic lesions were
previously diagnosed using a conventional skeletal survey (CSS). But
there is a deficiency in the sensitivity it offers, so it should only be
used when other modalities are unavailable. Whole body low dose has a
higher sensitivity in showing lytic bone lesions, where it reflects
signs of bone loss, especially in the spine and the pelvis [14]. On
the other hand, MRI has been established as the imaging modality of
choice when diagnosing MM by numerous studies [3, 4, 5, 13]. MRI can
show cell infiltration in the bone marrow which could indicate the
presence of MM. The IMWG recently updated the MRI indication for
diagnosing MM by increasing the number of focal lesions present on the
image that are greater than 5mm [14]. The MRI sequence for our case
showed a mass at the bottom of the spinal cord invading the cauda
equina, extending from the second dorsal vertebra all the way to the
sacrum (Fig.1, 2 ) . After MRI, to avoid post lumbar puncture
image changes, CSF analysis using lumbar puncture would be beneficial in
confirming meningeal involvement through detecting malignant plasma
cells [13]. In our case, CSF analysis showed atypical plasma cells.
Furthermore, we performed immunophenotyping of the CSF sample, which
revealed CD38, CD138, IGG kappa, and CD7 (Fig.4). There are multiple and
different approaches to treatment for MM. But since there have not been
a lot of CNS-involved MM cases, the treatment still doesn’t have
regulated guidelines. Therapy for these cases requires acting agents on
the MM and the ability to penetrate the blood-brain barrier (BBB)
[5]. The different treatment plans for MM without CNS metastasis
include chemotherapy such as bortezomib, thalidomide, lenalidomide, and
bendamustine; radiotherapy, which is ideal for the plasma cell neoplasms
are radiosensitive; and autologous stem cell transplant [5, 6, 7, 10,
13]. Bisphosphonates are pyrophosphate equivalents that are used as
osteoclast inhibiting agents [14]. They also have a proliferating
effect on the osteoblasts and osteocytes hindering cell death [7].
These changes result in fewer skeletal-related events such as
pathological fractures and spinal cord compression [3]. However,
bisphosphonates could induce renal function impairment and osteonecrosis
of the jaw [3, 7]. Bortezomib, which is a proteasome inhibitor,
limits osteoclastogenesis and helps to regulate the bone remodeling
feature of MM [6]. It is usually used alongside dexamethasone as a
part of the VD protocol [10, 11]. Immunomodulating agents such as
Thalidomide and Lenalidomide could be added to the protocol where they
will be named VTD or VRD respectively [10]. Our patient received 4
courses of VRD, followed by complete remission of the disease.
Autologous stem cell transplants (ASCT) have shown great promise in
increasing the progression-free survival and overall survival rate. A
recent retrospective study, conducted on 80 patients with extramedullary
multiple myeloma, where 13 patients received ASCT, showed higher
survival rates for patients receiving ASCT. The progression-free
survival rate was 46 and the overall survival rate was remarkably
greater than rates in patients who have not had ASCT[11]. In this
case, following chemotherapy, there was little to no trace of the
neoplastic cells in the bone marrow.