RESULTS
Autopsy reports classically document a “Final Diagnosis” that
describes cancer primary site, histologic findings, and tumor expansion
and metastases based upon an examination of all major
organs.9 If an autopsy report first documents the
presence of cancer post-mortem, documentation is reviewed to ensure that
no clinical cancer diagnosis was made prior. If no diagnosis is listed,
the case is identified “diagnosed at autopsy.”9Autopsy reports outline a succession of events that convey essential
information in order to provide the useful information regarding the
patient’s condition including but not limited to chain of events,
injuries, or complications. 10 In cases where cause of
death is not apparent despite a thorough autopsy, a judgment may be made
by the coroner.10 The functional definition of “cause
of death” is important to understand in the context of autopsy
reporting because cancer can be an incidental finding that could lead to
misreporting of cancer-related deaths.
Sesterhenn et al. reviewed the cases of 91 HNC-related deaths from 1968
to 2007 and showed distant metastases in 46.2% and second primary
tumors in 17.6% of the cases reviewed.11 Multiple
studies have revealed substantial rates of discrepancy between pre- and
post-mortem diagnoses often varying from 10% up to
40%.12 Another case report discusses two patients who
presented clinically with no evidence of disease and were considered
‘cured,’ but had significant distant spread of disease upon
autopsy.13 Misdiagnoses that may have altered patient
treatment course have been quoted to range anywhere from 2.4% to
10.7%.12
Of non-thyroid HNCs, laryngeal cancer is an uncommon subtype, and its
prevalence is decreasing over time.14 Despite this, it
was the most common non-thyroid HNC diagnosed upon autopsy in our study
and was the primary cause of death in half of these patients. It is
unlikely these patients were asymptomatic as 50% of tumors were stage 3
and 4; thus, some combination of hoarseness, odynophagia, otalgia, neck
lumps, or mechanical disruptions in swallowing or breathing would likely
be present. It is unclear why the prevalence of undiagnosed laryngeal
cancer was high in our study compared to other HNCs. It is unlikely
socioeconomic status is a major contributing factor as most of the
patients examined fell into the same middle-class stratum of annual
income. Rather than misdiagnosis or socioeconomic factors, it is
possible patients who participate in heavy tobacco and alcohol use,
well-known risk factors for laryngeal cancer, are less likely to seek
medical care for any number of biopsychosocial reasons. Smoking is
associated with reduced social support, decreased intrinsic view of
self-efficacy, low health-related motivation, and a decreased likelihood
to complete pharmacologic or psychological treatment
regimens.15 Considering 27.77% of the patients in our
study were over 70 years old, it is also plausible that primary care
physicians could interpret symptoms of non-thyroid HNC as part of the
natural aging process due to an unfamiliarity of these pathologies and
their clinical presentations.
In sum, 47.06% of patients with non-thyroid HNC-related deaths were
found in patients with stage 1 or 2 cancers, which raises concerns
regarding documentation. Currently, otolaryngologists do not consider
stage 1 and 2 HNCs to be highly lethal. These results appear to
contradict that sentiment. Although autopsy is a powerful tool in cancer
biology, delays in autopsy and refrigeration of body tissue can decrease
the integrity of the tumor due to tissue decomposition. In addition to
macroscopic changes to tumors, delays in autopsy allow for molecular
alteration which may change the morphology of cancer
cells.16 Though small, these changes could affect
tumor grading and lead to underreporting of disease severity.
Additionally, because of the underuse of post-mortem imaging techniques
if a full-body autopsy is not completed, it is conceivable that not all
metastatic sites of disease will be discovered and reported; as of 2008,
an autopsy was performed in under 10% of all deaths in the United
States.17
Scarce autopsies could further the possibility of underreporting
undiagnosed HNC. It is possible that stage 1 and 2 cancers have a
higher-than-expected death rate because autopsies are usually conducted
in instances of unknown causes of death and pathologists may assume
incidental findings as causes of deaths if no other obvious pathologies
are found. All these factors can contribute to underdiagnosis or
misdiagnosis of cancer severity, which could cause lower stages of
non-thyroid HNCs to appear more malignant.
Non-thyroid HNC is over 17 times
more likely to be designated as the primary cause of death compared to
thyroid cancer in patients with undiagnosed HNCs at autopsy. One
plausible explanation for this finding is that 50.00% of laryngeal
cancers found at autopsy were stage 3 or 4 while only 11.81% thyroid
carcinoma were stage 3 or 4. Patients with thyroid cancer had relatively
similar death rates in primary cause of death categories as the general
public.18 This data suggests thyroid cancer did not
contribute to the mortality of these patients and was an incidental
finding that may or may not had associated symptoms. It should be noted
that not all thyroid cancers are latent. Medullary, anaplastic, and
Hurthle cell thyroid cancers are often more aggressive in nature;
however, these cancers only contributed to 3.18% of the cancers
analyzed. We also found that patients over 70 years old were at lower
risk of thyroid related deaths than those under 50, likely because other
health issues such as cardiovascular disease are more common causes of
deaths in elderly populations. Conversely, non-thyroid cancer is often
more aggressive with poorer prognoses.19Consequentially, non-thyroid cancers are more likely to be the cause of
death than thyroid cancer.
Fewer patients with non-thyroid HNC were found at autopsy compared to
thyroid cancer, likely due to the higher prevalence of thyroid cancer
and decreasing incidence of HNC overall.20,21Our study found no identifiable
temporal trends in detection of non-thyroid cancers upon autopsy;
however, there was a discernible decrease in thyroid cancers diagnosed
at autopsy over time. This is likely due to increased screening and
biopsy of thyroid cancer in recent
decades.10 This study
demonstrates the malignancy of non-thyroid cancers and their prevalence
as the primary cause of death upon autopsy in patients previously
undiagnosed. These findings demonstrate the need for the medical
community’s awareness of their prevalence in asymptomatic patients and
the need for screening in those high risk for disease development or
progression.
There are inherent limitations within the dataset obtained from SEER
that includes miscoding and omitting data especially in variables such
as TMN staging and tumor size. This dataset has a limited number of
reviewable patients and autopsy reports that may or may not be
representative of the total population of the United States. Because the
SEER database only covers about 28% of the U.S. population, the results
may not be completely generalizable.22 In addition,
many of the variables within SEER have a significant number of data
points missing; therefore, non-statistically significant findings may
not be truly accurate.