Results
According to the original cohort based on registry data, 87 patients
below 15 years were diagnosed with a spinal tumor in Denmark from
January 1st, 1996 to December 31st,
2018.
17 patients were excluded due to misclassification, as they were not
classified as classical spinal tumors, being brain tumors, Langerhans
cell histiocytosis, lymphoma, hemangioma, hamartoma, sarcoma, and bone
sarcomas with location in the spinal cord. Further, 12 patients were
excluded due to missing records or insufficient data, (Fig. 2).
The final cohort of the present study included 58 patients aged 0-14
years diagnosed with a spinal tumor. 64% (37/58) had a prior
musculoskeletal diagnosis, and 89% (33) of these were a misdiagnosis.
Thereby a total of 57% (33/58) had a musculoskeletal misdiagnosis. The
majority (64%, 21/33) of the misdiagnoses were non-specific including
musculoskeletal pain (46%, 16/33), and accidental musculoskeletal
lesions, often evaluated at the emergency room (15%, 5/33) such as
torticollis, muscle strains, and sprains. A specific rheumatic
misdiagnosis occurred in 36% (12/33) and included arthritis,
arthropathy, osteomyelitis, discitis, inflammatory spondylopathy,
reactive arthritis, and scoliosis.
In Table 1 we compare the clinical characteristics: age, gender, tumor
type, metastases, treatment, and comorbidities of the group with versus
without a musculoskeletal misdiagnosis. There was no difference in
gender distribution between the two groups. Patients with a prior
misdiagnosis were older (median age 10.5 vs. 5.9, p=0.04). Most of the
tumors were low-grade tumors, present in 82% vs 68% (p=0.35).
Ependymoma was the most common type of tumor in both groups (found in
27% vs. 20%, p=0.56). Low-grade astrocytoma was slightly more
prevalent in the group with a misdiagnosis (24% versus 16%, p = 0.53),
whereas high-grade astrocytoma, glioblastoma, medulloblastoma and
primitive neuroectodermal tumor (PNET) occurred more often in patients
without a misdiagnosis (32% vs. 9%, p=0.002), Table 1. Metastases to
the brain were less frequent in the group with a misdiagnosis (9 % vs.
24%, p=0.15). Additional treatment was less prevalent in patients with
a misdiagnosis: 21% received steroids or pressure relieving operations
compared to 40% of patients without a misdiagnosis (p=0.15), and only
15% received chemotherapy compared to 40% of the patients without
misdiagnosis, (p=0.04). Comorbidity occurred less frequent in patients
with a misdiagnosis compared to those without (39% versus 60%,
p=0.18), mainly due to a lower frequency of CNS comorbidity, including
epilepsy and mental retardation, present in 6% with misdiagnosis and
24% without (p=0.15), Table 1.
In Table 2, we present a comparison of the clinical presentation for the
group with versus without a misdiagnosis, with pain and paresis as the
most common presentation in both groups. Musculoskeletal symptoms were
present in 100% of patients with a misdiagnosis versus 56% of patients
without (p= < 0.001). In the patients with a misdiagnosis the
most common presenting symptom was localized pain in the lower limb,
neck, and/or back, occurring in 81% compared to 28% of the patients
without a misdiagnosis (p < 0.001), Table 2.
Neurological symptoms were less common in patients with a misdiagnosis
(63%) compared to those without (96%; p=0.004), (Table 2).
Furthermore, general symptoms such as fatigue, fever, and weight loss
were less frequent in patients with a misdiagnosis (21% vs. 52%,
p=0.02). Physical findings were highly prevalent and did not differ
between the two groups, with abnormal neurological findings,
particularly paresis, sensory deprivation, and disordered reflexes,
being the most frequent (Table 2).
Mistreatment in the form of physiotherapy, chiropractor or painkiller
occurred only among the patients with a misdiagnosis (36%, p
< 0.001). Almost a third (27%) of the misdiagnosed children
had received prior physiotherapy treatment. The time from first symptom
until evaluated at the hospital (parental and primary care interval) did
not differ compared to the cases not receiving physiotherapy, being
respectively 60 days (IQR 22; 540, range 0;788), compared to 59 days
(IQR 13; 100, range 3;730), p=0.34. Though, when comparing to the
patients without a misdiagnosis they have a shorter interval with 27
days (IQR 4;91, range 0-880), p=0.10.
Table 2 and Fig. 3, provide a comparison of diagnostic intervals for
patients with and without a misdiagnosis. Patients with a misdiagnosis
experienced a longer total interval (time from onset of symptoms until
treatment) with a median time of 165 days (IQR 35;318), compared to 97
days (IQR 28; 176) for those without a misdiagnosis (p=0.07), mainly due
to longer parental and primary care intervals. Half of the patients
(52%) with a misdiagnosis had a total interval exceeding six months,
compared to one third (32%) of patients without a misdiagnosis
(p=0.18).
The first hospital doctor was a pediatrician in 60% of all cases.
However, for patients with a misdiagnosis, orthopedic doctors or general
doctors in the emergency room were the first hospital doctor in 21% of
cases, compared to zero cases for patients without a misdiagnosis
(p=0.02). A referral to a specialist occurred after the tumor diagnosis
was established in 79% of cases, resulting in a median specialist
interval of 0 days (IQR 0;1).
In order to further investigate any patterns or red flags in the group
with a musculoskeletal misdiagnosis we performed an analysis comparing
the 12 patients with a specific “rheumatic” misdiagnosis (including
arthritis, arthropathy, osteomyelitis, discitis, inflammatory
spondylopathy, reactive arthritis, and scoliosis) to the 21 patients
with a non-specific musculoskeletal misdiagnosis (including
musculoskeletal pain and accidental musculoskeletal lesions). Further
the 12 patients with specific “rheumatic” misdiagnosis were compared
to the 25 patients without a misdiagnosis, Supplemental Table S1. The
patients with a specific rheumatic misdiagnosis predominantly had
low-grade tumors (83%), and metastasis did not occur in this group.
High-grade tumors occurred in respectively 17% and 19% of the children
with misdiagnoses and in 32% of the children without musculoskeletal
misdiagnoses (p = 0.45). Pain as the first presenting symptom occurred
in 95% of the patients with non-specific misdiagnoses compared to 42%
in the group with specific rheumatic misdiagnoses (p<0.001).
The frequency of other symptoms and findings did not differ for the
children with specific versus non-specific misdiagnoses. When comparing
the diagnostic interval for these three subgroups we found an even
longer secondary care interval in the subgroup with a specific
misdiagnosis, including a long first hospital doctor interval of 128
days (IQR 13; 153), compared to 10 days (IQR 1; 74) for the subgroup
with non-specific misdiagnoses (p=0.10), and 7 days (IQR 1; 45) for the
group without a misdiagnosis (p=0.01).
The impact of a musculoskeletal misdiagnosis on overall survival is
illustrated in a Kaplan-Meier curve (Fig. 4). The group with a prior
misdiagnosis tended to have a higher 5-year survival of 83% (95% CI
63-92%), compared to 66% (95% CI 44-82%) for the patients without
musculoskeletal misdiagnoses (p=0.15). For the total cohort, 55%
achieved complete remission and 25% (15/58) died due to tumor or
treatment. The median duration of follow-up was 10.6 years (IQR 5.2;
14.7), being 8.8 years (IQR 7.1; 21.1) for children with misdiagnoses
and 11.3 (IQR 8.6; 12.6) years for the children without, p=0.45.
Sequelae were highly prevalent among all patients, reported in 63% with
a misdiagnosis and 76% of patients without a misdiagnosis (p=0.37).
Severe sequelae occurred in 42% of patients with a misdiagnosis and
56% of patients without (p=0.43). There was no significant difference
in the frequency of musculoskeletal sequelae when comparing the two
groups (24% vs. 20%, p=0.76). Similarly, there was no significant
difference in the frequency of central nervous system (CNS) sequelae
between the two groups (52% vs. 60%, p=0.60). The most frequent CNS
sequelae were paraplegia, paresis, sensory impairment, incontinence, and
decreased cognitive function.