Discussion
Laryngeal malignancies almost always arise from the surface epithelium
and thus, more than 95% are squamous cell carcinoma.[5] Similarly,
our results are consistent with the literature with an incidence of 90%
conventional SCC, 7.3% vSCC and 2.7 non-SCC laryngeal malignancies.
Verrucous carcinoma is the most common variant of SCC both in the
literature and in our series. In a review published in 2016, the
incidence of laryngeal verrucous SCC was reported to be 1-3.4%.[6]
In our study, the incidence of verrucous carcinoma within the entire
laryngeal malignancies is calculated as 2.3% (34/1497), which is
similar to the literature. Verrucous carcinoma mostly arises from the
glottic region and hence frequently can be diagnosed at the early
stages.[7] Furthermore, regional or distant metastasis is not
common. For these reasons, transoral laser surgery is often adequate
with excellent survival rates.[7] In the present study, 73% of the
patients had a T1a tumor, and 88% of tumors were localized in the
glottic region with an overall 5-years survival rate of 100%. No neck
and distant metastasis occurred in any of the patients in the study
group, thus for patients with pre-operative verrucous carcinoma
diagnosis, elective neck dissection is not necessary.
Laryngeal basaloid SCC is an aggressive variant of SCC which was first
described in 1986.[8,9] Laryngeal basaloid SCC is often diagnosed in
the supraglottic localization. Begum et al. detected the tumor in the
supraglottic localization in all of the patients (8/8)[10], and
Ereno et al in 86% (13/15).[11] In our patient group, the
supraglottic region is the most common localization of the tumor (82%).
Published studies indicated that neck metastasis occurs up to 50-70% in
patients with basaloid SCC.[12,13] In our study, neck metastasis was
observed in 46.4% of the patients. Due to the higher tendency to
regional and distant metastasis, lower survival rates have been
published. In a study published in 2008, 3 and 5-year overall survival
of 15 patients reported as 50% and 38.5%, respectively.[11] In our
study, 5-year disease-specific survival was determined as 69.9%. While
the survival rate is 100% for the early stages, a decline to 54.5% is
observed for late-stage tumors.
Spindle cell carcinoma was first described by Virchow in 1863 and in
1933 Figi described the entire pathological details.[14] The most
common origin of the spindle cell carcinoma is the larynx.[15] Even
though the prognosis is directly related to the stage, spindle cell
carcinoma is an aggressive tumor.[14] In the present study,
according to the survival rates, spindle cell carcinoma is the variant
with the worst prognosis.
Laryngeal papillary SCC was first described in 1999 by Thompson et
al.[16] including 104 cases as a variant of SCC with a good
prognosis. Similar to the literature, survival rates are also excellent
in our study. Even though, our follow-up period is inadequate to give
5-years survival rates, both of our patients are disease-free at their
17th and 28th-month follow-up. In a
study in 2015, 370 patients were evaluated by using the Surveillance,
Epidemiology, and End Results (SEER) Program, and the overall incidence
within entire laryngeal malignancies was calculated as 0.5%.[17] In
the present study, an incidence of 0.1% was calculated. High-risk Human
Papilloma Virus (HPV) strains are thought to play a role in the etiology
of the papillary variant of SCC.[18,19] Our lower rates can be
explained by the low incidence of these strains in our country.[20]
Due to the retrospective nature of our study and lack of HPV-DNA or p16
screening, we can’t make a definite interpretation.
Laryngeal lymphoepithelial carcinoma is a variant of SCC that has a
resemblance to undifferentiated non-keratinized (WHO type 3)
nasopharyngeal carcinoma and a high affinity to neck
metastasis.[5,21] Similar to the literature, neck metastasis was
observed in 75% of our patient group. According to SEER data in which
16 patients were evaluated, overall and disease specific 5-years
survival of this variant was 58,8% and 63%, respectively.[22] The
overall and disease specific 5-year survival in our study was assessed
as 50% and 75%, which was slightly better compared to this study.
However, due to our low number of patients (4), a comparison with the
literature would not be suitable.
Acantholytic SCC was classified as a vSCC until 2017, however, after
2017 this variant was included in the conventional laryngeal SCC
group.[5,23] The evaluation of the patients in this study group was
done with the previous classification system, thus 17 patients were
diagnosed with the acantholytic variant. Overall 5-years survival was
calculated as 72.8% and neck metastasis was observed in 31.3% of the
patients who were treated with primary surgical methods. Our results
show similarity to prognosis and neck metastasis rates of the classical
laryngeal SCC.[24,25]
Laryngeal adenosquamous carcinoma is a vSCC with both glandular and
epithelial differentiation. Previous studies of this variant show neck
metastasis up to 75% and distant metastasis up to 25% of the
cases.[5] Adenosquamous carcinoma is the vSCC with one of the worst
prognosis, and previous 5-years survival studies show around 30-50%
survival rates.[5] Controversially, in our study, the 5-years
survival rate for adenosquamous carcinoma is 83.3%. The explanation for
this great difference can be explained by the absence of any patients
with distant metastases at the time of diagnosis in this pathological
subgroup, which will also be mentioned in the limitation of the study.
Due to the absence of this feature, which is a bad prognostic factor,
better survival rates were calculated.
We found that some of the patients included in this study had a
preoperative pathological diagnosis, not vSCC, but conventional SCC with
the incidence of 38.5-100% according to the histological subtype. It is
possible to detect pathological subgroup changes in the operated
patients, but it is not possible to detect this situation in the patient
group who underwent non-surgical treatment. For this reason, several
patients who should be in the vSCC group are considered as classic SCC,
and treatment and follow-up planning can be made with this information.
Another result of this condition is the survival data of our study; the
survival data of some pathological subgroups were observed better than
the literature. One of the possible causes of this condition may be that
the patients with poor prognostic indicators, inoperable tumors and
distant metastases receive non-surgical treatments, and the diagnosis of
these patients should be reported as conventional SCC, not vSCC. Thus,
the patient group in our study may have consisted of patients with a
relatively good prognosis.
The difference between the diagnostic and definite pathology results can
be explained by the heterogeneity of the tumors, which creates areas
that do not contain the vSCC. Although smaller specimens are adequate
for the malignity diagnosis, sub-typing is not always possible. A small
biopsy is usually taken for diagnosis of laryngeal cancer. Because large
biopsy fragments can cause bleeding, edema, and associated airway
obstruction. In patients with small lesions planned to be treated with
primary RT, permanent vocal cord damage and permanent quality of voice
may occur after treatment. It can be concluded from this study that
small punch biopsies may not be sufficient for the diagnosis of vSCC.
While evaluating the patients for adjuvant therapies, along with the TNM
stage of the tumor, pathological subgroup change possibility should also
be taken into account. Especially, the worse prognosis and high
metastatic potentials of spindle cell carcinoma and basaloid type SCC
should be kept in mind. Patients who are diagnosed with these two
variants should be followed-up more carefully, and the physicians should
be more skeptic if any recurrence suspicion is present.
The first limitation of our study is the retrospective design. The
clinical and pathological staging of the tumors was reported by using
the 7th Edition of The American Joint Committee on
Cancer (AJCC), which was renovated by the 8th Edition
in January 2018. Secondly, the vast majority of the patients who were
included in the study are patients who were surgically treated. Thus,
some of the patients with distant metastasis at the time of the
diagnosis might be missed out. For this reason, the survival rates might
be lower than our calculated results. Even though prospective studies
can be designed for better prognosis and survival rate analysis,
differences between pre-operative and definite pathology results will
always cause under-diagnosis of variants.