Keywords
Glottic oncology - infrahyoid neck imaging - neck imaging
Introduction
Laryngeal cancer forms 1% of all diagnosed cancers. In India, its incidence varies
from 1.26 to 8.18 per 1,00,000 individuals varying in different demographic distributions.
Men are invariably more affected than women, and it is the seventh most common cause
of cancer in Indian men.[1]
The association of laryngeal cancer is well established with tobacco. The present
study is conducted in demographic belt in West India where tobacco consumption is
higher than the national average, and hence, laryngeal cancer is an important ailment
in the given demographics.[1],[2]
Laryngeal cancer is a potentially treatable disease, and it is one of the few malignancies
where a surgical approach is not a primary treatment protocol and is reserved for
the locally advanced disease. After the 1991 publication of the veterans administration
(VA) laryngeal trial,[3] a paradigm shift came in the treatment protocol of laryngeal cancer. Where before
that time, a total laryngectomy was the primary treatment for most patients with T3–T4
laryngeal cancer, after that trial organ preservation along with more conservative
treatment such as concurrent chemoradiotherapy was started to be preferred as the
first-line treatment.[4]
Thyroid cartilage invasion has been defined as one of the crucial criteria which determine
the need for total laryngectomy in a case of laryngeal cancer. According to the current
American Joint Committee on Cancer guidelines, where a minor cartilage involvement
defines T3 disease which may be treated with an organ preservation approach, a major
thyroid cartilage erosion or destruction defines T4 disease which warrants for a more
radical surgical approach. Although a number of recent trials suggest possible roles
of chemoradiotherapy even in advanced stages, it is yet to be accepted as a primary
treatment protocol in most institutions including ours.[4],[5],[6]
In the present era, multidetector computed tomography (MDCT) forms the backbone of
head and neck oncological imaging due to its superior accuracy in detection of various
parameters such as soft-tissue lesions, underlying bony involvements, better depiction
of nodal status, and comprehensive approach in detecting disease extension due to
its multiplanar reconstructive capability. In addition, phonation and Valsalva maneuver
imaging help detect the presence and extent of smaller glottic lesions.[7]
However, MDCT has long been accused of a less accurate analysis of the thyroid cartilage
involvement in laryngeal cancer by often overestimating the cartilage involvement.
The MDCT results may lead to a clinicoradiological dilemma which often results in
the patient being over staged and hence subjected to surgery whereas a more accurate
preoperative staging could have helped treat the patient with organ preservation techniques.[8]
The present study is conducted to address this constant dilemma and aims at analyzing
the accuracy of MDCT in detecting thyroid cartilage invasion in laryngeal and hypopharyngeal
cancer in a tertiary center. The MDCT results were compared with histopathological
examination (HPE) results which were considered as gold standard.
Materials and Methods
The present study was conducted in a tertiary hospital in Western India which is located
in a high tobacco consumption belt.
Study design
After due Institutional Ethical Committee approval, a retrospective analysis was done
for patients presenting as T3 and T4 stage of laryngeal and hypopharyngeal cancers
in the tertiary teaching institute from April 2016 to March 2017.
The study comprised of patients who were clinically and radiologically diagnosed as
T3/T4 laryngeal or hypopharyngeal disease and underwent laryngectomy and HPE evaluation
at our institute. The postoperative HPE results were reviewed for each patient and
were taken as gold standard for evaluation of the accuracy of MDCT in detecting preoperative
thyroid cartilage involvement.
We excluded the patients from our study who did not undergo laryngectomy at our institute.
Furthermore, the patients who had taken chemotherapy or radiotherapy before the surgery
were excluded from our study.
The MDCT results were retrospectively reviewed by a single radiologist (the author)
who was blind to the pathological diagnosis. The histopathological results were obtained
from the hospital's database and reviewed to be compared with MDCT results.
Multidetector computed tomography protocol and result analysis
Protocol
The study was performed with a 128 Slice Optima CT 660 (Wipro GE Healthcare Pvt. Ltd.)
machine. The procedure was briefly explained to the patient, and detailed informed
consent was obtained. An initial topogram of the neck was obtained, and further series
were planned accordingly. With the patient in supine position, noncontrast 5 mm thick
contiguous axial MDCT sections of the neck were performed from the skull base to aortic
arch, subsequently followed by intravenous administration of 80 ml nonionic iodinated
contrast medium (300 mg iodine/ml - iohexol) using an automated power injector. Phonation
images were acquired subsequently. The axial images were reconstructed to procure
sagittal and coronal reformations of high quality, with reconstructed sections as
thin as 1.25 mm obtained through the region of interest.
Multidetector computed tomography analysis
The analysis aimed to establish the efficacy of MDCT comprehensively in detecting
thyroid cartilage invasion in its various stages, thereby staging laryngeal cancer
along with the individual accuracy of various appearances of the involved cartilage
in demarcating the disease stage.
Cartilage involvement
The results of thyroid cartilage assessment were marked as no involvement, minor involvement,
and major involvement.
Cortical irregularity and erosion of only inner cortex were considered minor involvement.
Asymmetrical sclerosis, erosion through both inner and outer cortices, lysis, and
presence of enhancing lesion on both sides of cartilage depicting extralaryngeal spread
through the cartilage were considered the criteria for major cartilage erosion.[5]
Minor cartilage involvement was seen as a depicter of T3 disease while major cartilage
erosion was considered as a marker of T4 disease.[2],[4] Criteria are schematically depicted in [Figure 1].
Figure 1: Schematic diagram depicting types of thyroid cartilage
involvement in laryngeal cancer
Histopathological evaluation
The histopathological results after total laryngectomy were reported as no involvement,
superficial involvement, and cartilage involvement by the institute's Pathology Department.
Statistical analysis
Statistical analysis was made using Microsoft Excel and MedCalc Software. The results
of MDCT in evaluating various types of cartilage involvement in comparison to the
corresponding pathological diagnosis were calculated in terms of sensitivity, specificity,
positive predictive value (PPV), and negative predictive value (NPV).
It is prudent to understand that this study is aimed at addressing the clinicoradiological
tussle over the overdiagnosis of cartilage invasion by MDCT in laryngeal cancer and
not regarding the primary pick up ability of MDCT in this situation; therefore, while
analyzing the statistical data, it is the PPV and NPV of MDCT that takes the front
seat rather than sensitivity and specificity.[8]
Results
On retrospective analysis of data, we found that 61 cases of laryngeal or hypopharyngeal
carcinoma had presented to our department for MDCT neck evaluation in the given time.
Out of this 61, 22 cases fulfilled our inclusion criteria and were included in the
study.
Demographics
The study group demographic profile is depicted in [Table 1] and [Table 2].
Table 1: Age distribution
Table 2: Sex distribution and association with tobacco usage
Supraglottic involvement was the most common presentation seen in 72.72% patients.
Most cases presented with laryngeal component of disease, only two cases (9.0%) showed
hypopharyngeal involvement only with no laryngeal component [Table 3].
Table 3: Primary site of involvement
Cartilage involvement
A total number of cartilages involved as seen by MDCT were 15 while only 10 were pathologically
confirmed to be involved.
Computed tomography (CT) found minor cartilage erosion in only three cases out of
which pathology confirmed superficial erosion in one case and no erosion in the remaining
two cases. Major cartilage invasion as depicted by various findings as defined in
the criteria above was found in 12 cases on MDCT. Out of these, eight cases were pathologically
confirmed to have major thyroid cartilage invasion, and in four cases, the cartilage
was found free from the lesion or to be having only superficial erosion. There was
only one false-negative case in which cartilage invasion was confirmed on HPE but
missed by MDCT.
The statistical results of MDCT in detecting minor and major cartilage involvement
are depicted in [Table 4] and [Table 5].
Table 4: Statistical analysis of multidetector computed tomography results in detecting
minor cartilage invasion
Table 5: Statistical results of multidetector computed tomography in detecting major
cartilage erosion
In analyzing accuracy of individual CT appearances of a major invasion as in erosion
of both inner and outer cortices and lysis, we found that these features were shown
in 11 cases on MDCT out of which 8 were pathologically confirmed to be T4A disease
while the rest were downgraded to T3 disease by pathology. The presence of enhancing
soft tissue on both sides of the thyroid cartilage and extralaryngeal spread was seen
in seven cases on MDCT out of which five were pathologically proven to be T4A disease
and two were downgraded to T3 disease. Statistical results of individual morphological
findings in depicting T4A staging are tabulated in [Table 6]. The overall results of MDCT in detecting all types of cartilage invasion are shown
in [Table 7].
Table 6
Accuracy of individual morphological features on multidetector computed tomography
in detecting T4A disease
|
Morphological character on MDCT depicting major cartilage involvement
|
TP
|
TN
|
FP
|
FN
|
Sensitivity (%)
|
Specificity (%)
|
PPV (%)
|
NPV (%)
|
|
Depicted as number of cases. MDCT – Multidetector computed tomography; PPV – Positive
predictive value; NPV – Negative predictive value; TP – True positive; TN – True negative;
FP – False positive; FN – False negative
|
|
Sclerosis
|
2
|
6
|
1
|
9
|
18.18
|
85.71
|
66.67
|
40
|
|
Through and through invasion
|
8
|
10
|
3
|
1
|
88.89
|
76.92
|
72.73
|
90.91
|
|
Extralaryngeal spread
|
5
|
14
|
2
|
1
|
83.33
|
87.50
|
71.43
|
93.33
|
Table 7: Final statistical results of multidetector computed tomography in detecting
thyroid cartilage invasion (both minor and major)
Multidetector computed tomography in detecting stage of laryngeal cancer
It is important to remind that while thyroid cartilage invasion is a very important
criteria for T-stage detection in laryngeal cancer, it is not the only criteria for
demarking these two stages, and many other CT findings play a crucial role such as
the involvement of preepiglottic and paraglottic areas in T3 disease and the invasion
of strap muscles, the thyroid gland, and esophagus in T4A disease. Therefore, it is
worthwhile to analyze the overall capacity of MDCT in detecting the disease stage
which is ultimately the actual guide for therapeutic results.
It was observed that out of eight cases marked as T3 disease by MDCT, four were confirmed
by pathology while the other four were downgraded to T2 disease by pathology. CT demarked
14 cases to be of T4A disease out of which 11 were confirmed by pathology and 3 were
downgraded to T3 disease. A total of 7 out of 22 cases were downgraded in staging
by pathology [Table 8].
Table 8: Accuracy of multidetector computed tomography in detecting T4A disease as
compared to final histopathological results
Representative cases are depicted in [Figure 2] and [Figure 3].
Figure 2: (a) Axial contrast-enhanced computed tomography soft-tissue window images
show enhancing lesion in the right glottis eroding through the right thyroid cartilage
with extralaryngeal spread. (b) Bone window image shows complete lysis of the right
lamina of thyroid cartilage. Major cartilage invasion was confirmed by histopathological
examination in this case
Figure 3: (a) Axial contrast-enhanced computed tomography soft-tissue window shows
enhancing mass lesion eroding through the right lamina of thyroid cartilage. (b) Bone
window image shows a lytic defect in the right lamina of thyroid cartilage at this
level. However, on histopathological examination, major cartilage invasion was not
confirmed
Discussion
Laryngeal cancer forms about one-fourth of the diagnosed head and neck cancers in
India. It has a strong male predominance as per the Indian Cancer Registries, being
one of the top ten cancers to affect Indian men. In our study, we made a similar observation
with 88% of the study group consisting of males. Similar observations were made by
Sharif et al.[9] and by Bobdey et al.[1]
Laryngeal cancer is a disease of the elderly with most cases presenting between 50
and 70 years of age. The mean age in our study group was found to be 54.36 years.
As depicted in literature, we also found a strong association with tobacco chewing
in our study, in as many as 63.63% patients.[1],[2]
The current management protocol of advanced laryngeal cancer is guided by the American
Joint Committee for Cancer which has made preoperative evaluation of laryngeal cancer,
an essential requirement for the concerned oncologist, and a meticulous responsibility
for the concerned radiologist. Major thyroid cartilage erosion defines T4 disease
while Minor cartilage erosion defines T3 disease, both having different management
protocols. It has been long established that a major thyroid cartilage erosion defines
higher rate of recurrence and significantly reduces the chances of success of radiotherapy,
thereby implying that only conservative measures will not suffice, and in this case,
surgical treatment becomes a mandatory consideration subject to resectability.[2],[3],[4]
A vast window has been found in depicting the accuracy of CT in detecting thyroid
cartilage involvement which ranges from 7% to 83% sensitivity and 40%–100% in the
early studies conducted by Becker et al.[10] Over the years and even with the advent of various techniques, the variation still
remains. In a recent study, Hartl et al.[11] found CT's sensitivity to be as low as 10.5% and PPV to be 13% in detecting thyroid
cartilage involvement in mid to advanced laryngeal cancers.
In our study, we found that the PPV of CT was best in detecting major cartilage invasion,
i.e., 66.67%, where a definite erosion of the outer cortex and extralaryngeal spread
are helpful criteria for diagnosis. This was followed by the PPV for diagnosing all
types of cartilage involvement, i.e., 60.00%. The major observation from this study
was the poor results of CT in diagnosing minor cartilage erosion with a PPV of only
33.33%. The closest similarity with our study results was depicted by Li et al.[8] who also analyzed the involvement of cartilage on similar parameters of minor, major,
and overall involvement [Table 9].
Table 9
Comparison of positive predictive value of the present study with study of Li et al. with similar parameters of analysis
|
PPV in minor thyroid cartilage erosion
|
PPV in major thyroid cartilage erosion
|
PPV in overall thyroid cartilage erosion
|
|
Present study (%)
|
33.33
|
66.67
|
60.00
|
|
Study by Li et al. (%)
|
30
|
78
|
63
|
Other studies which comprehensively studied both major and minor cartilage involvement
together also show a large range in their results. A systemic review conducted by
Adolph et al.,[12] analyzed the variability of PPV of MDCT in thyroid cartilage invasion in 3 series,
and showed a range of 44%–80% for PPV and 80%–100% for NPV. Koopmann et al.[13] found a PPV of 76% and an NPV of 69% for MDCT in the said finding.
Analyzing individual morphological parameters, major cartilage erosion was found to
be the most sensitive criteria for depicting T4 disease while extralaryngeal spread
was the most specific criteria. We found a low accuracy for sclerosis in depicting
cartilage involvement. Similar observation was made by Beitler et al.[4] and Fernandes et al.[14] who emphasized on the importance of extralaryngeal spread as a specific parameter
and could not depict sclerosis as a strong parameter for depicting T4 disease.
On overall comparison of preoperative staging by MDCT to the final histopathological
analysis, as many as 31.8% of cases were downgraded by pathology in T-staging. A therapeutically
important observation was that 27.27% of cases were downgraded by pathology from T4A
to T3 disease which meant that >1/4th patients of the study group were preoperatively
overstaged and could have been treated by organ preservation instead. This large discordance
of CT and pathology highlights the clinical dilemma of why the MDCT cannot provide
reliable results even with the advent of a much better technology over the years.
The answer is somewhat explained by the heterogeneity of appearance of thyroid cartilage
over age or with the amount of fatty content within the marrow. The thyroid cartilage
starts to ossify at adolescence and may continue up to the end of the 7th decade.[15] The nonossified or partially ossified thyroid cartilage may create doubt regarding
subtle areas of erosion, hence reducing the accuracy of MDCT. Hence, a doubtful region
in the unossified cartilage may be mistaken for a minor involvement, thereby providing
the lower PPV of CT for minor cartilage involvement. However, it is encouraging to
know that the ossified thyroid cartilage is more likely to be involved by the tumor.[2],[8] The other striking reason remains peritumoral inflammatory changes or periostitis
in laryngeal cancers which may create a false impression of cartilage involvement,
especially in cases of asymmetrical sclerosis on MDCT.[16]
All these reasons and the wide spectrum of results over time have forced both clinicians
and radiologists to look beyond MDCT; however, no solution which is both accurate
and practical is at hands as of now. Magnetic resonance imaging (MRI) offers a higher
sensitivity of 89% and NPV of 92%–96%, but along with technical difficulties, it offers
a lesser specificity and PPV in results due to being unable to differentiate between
peritumoral inflammation and cartilage involvement by tumor, both of which appear
as T2 hyperintensities.[16] Fluorodeoxyglucose-positron emission tomography has a limited role in pretreatment
imaging in laryngeal cancer which is mostly aimed at locating distant metastasis.
Its lack of accuracy in assessing lesions of smaller sizes makes it a less likely
replacement for CT or MRI in preoperative assessment of laryngeal cancer.[17] Recent study by Kuno et al.[18] comparing the results of CT with dual-energy CT (DECT) has shown promising results
in thyroid cartilage involvement in squamous cell carcinomas of larynx and hypopharynx.
A significant increase of PPV from 46% to 86% and specificity from 70% to 90% was
shown by addition of iodine overlay images of DECT as compared to CT neck. Although
this may pave the way for future diagnostics, the limited availability of DECT makes
it almost nonpractical option in today's diagnostic oncology in India.
The take-home message for the radiologist here is that detecting thyroid cartilage
invasion in the given scope of diagnostic modalities today is a tough and not very
rewarding exercise. A combination of expertise and meticulous assessment is required
to make the best out of the present opportunities. For the clinician, it is important
to remember that pretreatment thyroid cartilage invasion is though crucial but not
the only criteria for detecting staging of the disease. A myriad of factors such as
tumor bulk, other indicators of local spread, laryngoscopic examination findings,
clinical vocal cord-related symptoms, comorbidities, and therapeutic availability
and expertise should be kept in mind before making the decision regarding final therapeutic
approach.
Limitations of study
Major limitation of the current study is the small sample size as only advanced stage
patients were taken up for surgery at our institute. A larger prospective study is
required for more efficient results.
Conclusion
A relatively low PPV for thyroid cartilage invasion in advanced laryngeal cancer depicts
overestimation and overstaging of laryngeal cancer by MDCT, thereby suggesting that
many patients are inadvertently subjected to laryngectomy when an organ preservation
approach could have been used. Although far from perfect, MDCT offers a comprehensive
and most practical preoperative diagnostic assessment as of now. It is the need of
the hour to develop improved methods for differentiating between T3 and T4 stages
in advanced laryngeal cancer. A multidisciplinary approach and clinicoradiological
correlation seems the most rewarding option in the present times.
