Airidas Brazlauskas1*, Gabija Gintautaitė1, Jolita Gibavičienė2, Ignas Karnas2
1Faculty of Medicine, Vilnius University, Vilnius, Lithuania
2 ENT, Head and Neck Surgery and Oncology Department, National Cancer Institute,
Abstract
Background: Sarcomatoid or spindle cell carcinomas are rare malignancies which are considered as a poorly differentiated variant of squamous cell carcinoma composed of neoplastic cells that have a mesenchymal or sarcomatoid phenotype. Spindle cell carcinomas are an exceptionally rare occurrence in the larynx.
Case report: 53-year-old male was presented to the emergency department with severe dyspnea. Upon examination, a growth, completely blocking the airway was found. An emergency tracheostomy was performed, and a biopsy was taken. Histological features were not specific and differential diagnosis involved sarcoma and sarcomatoid carcinoma. 2 cycles of induction therapy were given, which generated a positive response. Transoral laser microsurgery resection with selective neck dissection was performed successfully. Post-operative histology confirmed spindle cell carcinoma and that resection margins were tumor-free. Post-operative radiotherapy was given, because of the following risk factors: poor differentiation degree and more than 2 positive lymph nodes.
Discussion: Spindle cell carcinoma is a poorly differentiated variant of squamous cell carcinoma and morphologically resembles sarcoma. The importance of a well-taken biopsy should be highlighted, as histological evaluation may be difficult, leading to misdiagnosis. Due to the very low incidence rate of sarcomatoid carcinoma of the larynx, there is no clear consensus for the most optimal treatment approach. Surgery is often the main treatment method; however, each case must be thoroughly examined on multidisciplinary tumor-boards to devise an optimal treatment plan.
Keywords: Laryngeal sarcomatoid carcinoma; Spindle cell carcinoma of the larynx; Transoral laser microsurgery; Induction chemotherapy.
Journal of Medical Sciences. May 18, 2020 - Volume 8 | Issue 16. Electronic-ISSN: 2345-0592
111
Medical Sciences 2020 Vol. 8 (16), p. 111-119
Uncommon laryngeal tumor. A case of spindle cell carcinoma of the
larynx
Airidas Brazlauskas
1*
, Gabija Gintautaitė
1
, Jolita Gibavičienė
2
, Ignas Karnas
2
1
Faculty of Medicine, Vilnius University, Vilnius, Lithuania
2
ENT, Head and Neck Surgery and Oncology Department, National Cancer Institute,
Abstract
Background: Sarcomatoid or spindle cell carcinomas are rare malignancies which are considered as a poorly
differentiated variant of squamous cell carcinoma composed of neoplastic cells that have a mesenchymal
or sarcomatoid phenotype. Spindle cell carcinomas are an exceptionally rare occurrence in the larynx.
Case report: 53-year-old male was presented to the emergency department with severe dyspnea. Upon examination,
a growth, completely blocking the airway was found. An emergency tracheostomy was performed, and a biopsy was
taken. Histological features were not specific and differential diagnosis involved sarcoma and sarcomatoid carcinoma.
2 cycles of induction therapy were given, which generated a positive response. Transoral laser microsurgery resection
with selective neck dissection was performed successfully. Post-operative histology confirmed spindle cell carcinoma
and that resection margins were tumor-free. Post-operative radiotherapy was given, because of the following risk
factors: poor differentiation degree and more than 2 positive lymph nodes.
Discussion: Spindle cell carcinoma is a poorly differentiated variant of squamous cell carcinoma and morphologically
resembles sarcoma. The importance of a well-taken biopsy should be highlighted, as histological evaluation may be
difficult, leading to misdiagnosis. Due to the very low incidence rate of sarcomatoid carcinoma of the larynx, there is
no clear consensus for the most optimal treatment approach. Surgery is often the main treatment method; however,
each case must be thoroughly examined on multidisciplinary tumor-boards to devise an optimal treatment plan.
Keywords: Laryngeal sarcomatoid carcinoma; Spindle cell carcinoma of the larynx; Transoral laser microsurgery;
Induction chemotherapy.
Journal of Medical Sciences. May 18, 2020 - Volume 8 | Issue 16. Electronic-ISSN: 2345-0592
112
Introduction
Laryngeal spindle cell carcinoma (LSpCC) is a
rare variation of squamous cell carcinoma (SCC)
which was first characterized by Virchow in
1863 (1). At that time it was considered as a dual
malignancy (carcinosarcoma), later in 1933 Figi
decisively described the tumor (2). This
malignancy is an uncommon form of divergent
differentiated SCC, which contain elongated
(spindle) epithelial cells and simulates a sarcoma
(3). LSpCC has a lot of different names and is
usually called a sarcomatoid carcinoma,
pseudosarcoma, pleomorphic carcinoma, and
sarcomatous carcinoma (4). The most common
site of this type of cancer, which can be seen in
about half of all cases of spindle cell carcinoma
of the head and neck, arises in the larynx and
usually affects the glottic area (4,5). Therefore,
common simultaneous findings in LSpCC are
changes in voice, airway obstruction, difficulties
in breathing and swallowing, cough, and foreign
body sensations in the throat (6,7). Other typical
locations are the oral cavity and pharynx,
however, it is important to mention that it can
occur almost anywhere in the body, for example,
skin, lungs, breasts and it decides what
symptoms will appear to the patient (2,4).
This tumor has a specific appearance
of a cumbersome pedunculated mass, mostly
with a surface of ulcers covered with exudate (8).
Histologically, LSpCC is biphasic and consists
of squamous cell component in the superficial
layer that may be dysplastic, carcinoma in situ,
or invasive; and a spindle cell component which
locates in the stroma and may incorporate osteo-
or chondrosarcomatous elements (9). Although
initial reports claim that LSpCC is a collision
malignancy, there are significant pieces of
evidence that advocate this tumor being
monoclonal (2). The sarcomatous component
features cells with increased vimentin and
decreased keratin expression, failure in intercell
adhesion, no basement membrane, and
production of collagen, coherent with metaplasia
to a mesenchymal phenotype (10). However, this
type of tumor is a difficult challenge to the
pathologist due to the significant morphological
and immunohistochemical overlap with other
various types of spindle cell tumors (4).
Laryngeal spindle cell carcinoma is
observed mostly in middle-aged to elderly men
and is strongly associated with tobacco and
alcohol usage (11). It is known that in the
majority of cases human papillomavirus
infection is not detected (12). Studies have also
shown that radiotherapy is not a causative factor
in this kind of tumors, however, malignancies
arising in patients who received radiotherapy
appear to have a more aggressive development
(9). Due to the affection of glottis, hoarseness is
the most prevalent complaint (10,11). Prognosis
depends on many factors, which include location,
tumor (T) stage, the existence of necrosis,
previous radiation, and lost epithelial markers‘
immunoexpression (9).
In this article, we report a 53-year-old
man who presented with severe dyspnea due to
an exophytic tumor completely blocking the
airway, radical treatment of malignancy, and
successful patient’s recovery.
Journal of Medical Sciences. May 18, 2020 - Volume 8 | Issue 16. Electronic-ISSN: 2345-0592
113
Case report
A 53-year-old male was presented to the
emergency department with severe dyspnea. On
admission, the patient reported that he noticed a
mass on the right side of the neck, which
appeared about 12 months ago. The patient has
been experiencing hoarseness for 3 months and
shortness of breath for the past week. The patient
admitted to being a chronic smoker and a regular
alcohol consumer.
Upon physical examination, a 1.5 cm
lymph node was palpated in the II zone on the
right side of the neck. An exophytic tumor,
completely blocking the airway was visualized
during fiberoptic endoscopy. It was decided to
perform an emergency tracheostomy under local
anesthesia. During the surgery, a biopsy was
taken for histological assessment. A pathologist
comment was received, that the histological and
immunohistochemical features of the tumor
biopsy are not specific and differential diagnosis
would be between sarcomatoid carcinoma and
sarcoma. No specific immunohistochemical
features to melanoma or thyroid carcinoma were
found. As shown in Figure 1, the magnetic
resonance imaging of the head and neck
displayed a 22 x 30 x 45 mm size supraglottic
tumor. The case was discussed on the
multidisciplinary tumor-board, due to the tumor
being exophytic, growing on a pedicle, with no
clear invasion to the surrounding tissue, it was
decided to start induction chemotherapy with
Docetaxel-Cisplatin-Fluorouracil regimen and to
re-evaluate the patient after 2 cycles.
After the induction chemotherapy, a
magnetic resonance imaging of the head and
neck was repeated. It showed a positive response
to treatment, as the tumor had reduced in size to
16 x 24 x 25 mm. The tumor was also visualized
with fiberoptic endoscopy (Figure 2). After the
reevaluation, it was decided to perform a
transoral laser microsurgery resection of the
tumor with selective dissection of II-IV level
lymph nodes on the right side of the neck. The
post-operative histology confirmed that resection
margins are tumor-free. Out of 18 lymph nodes
from the neck dissection, 12 were reactive and 6
showed local fibrosis, which was likely
chemotherapy-induced. The final diagnosis, in
this case, was supraglottic poorly
differentiated/undifferentiated sarcomatoid
(spindle cell) carcinoma T2N2bM0 IVa stage.
Due to risk factors of poor differentiation degree
and more than 2 positive lymph nodes –
postoperative radiation therapy was given.
The patient was evaluated 1-month
post-surgery. No new complaints were
expressed. Upon physical examination, scars
were seen after neck dissection and tracheostomy
(Figure 3). The fiberoptic endoscopy showed no
signs of tumor recurrence (Figure 4).
Journal of Medical Sciences. May 18, 2020 - Volume 8 | Issue 16. Electronic-ISSN: 2345-0592
114
Figure No.1. The tumor visualised by head and neck MRI.
Figure No. 2. Fiberoptic endoscopy performed after induction chemotherapy.
Journal of Medical Sciences. May 18, 2020 - Volume 8 | Issue 16. Electronic-ISSN: 2345-0592
115
Figure No. 3. Scars after tracheostomy and selective neck dissection.
Figure No. 4. Fiberoptic endoscopy 1-month post-surgery.
Journal of Medical Sciences. May 18, 2020 - Volume 8 | Issue 16. Electronic-ISSN: 2345-0592
116
Discussion
LSpCC is a rare biphasic tumor of the head and neck
which contains sarcomatoid proliferation of
pleomorphic spindle shape cells and SCC (13). It is
reported that LSpCC incidence is less than 1% of all
laryngeal malignancies which is why it is difficult
to find reliable guidelines for this tumor’s treatment
(10). Males take account of approximately 87,2% of
LSpCC cases, while a male-to-female ratio is 7:1,
although, in other studies, it is ever bigger (10:1 or
13:1) (2,10,11). The mean age of diagnosis of this
pathology is 57 (our patient was 53-years-old) and
most studies claim that it reaches the peak in the 6
th
and 7
th
decade (4,14).
Main risk factors that are acknowledged
to predispose this disease are smoking, usage of
alcohol, and poor oral health (4). A lot of case
reports claimed a history of radiation exposure to be
a risk factor for this malignancy, however, there is
no conclusive evidence to confirm this hypothesis
(7). Our patient had long-lasting smoking and using
alcohol history which means that his oral health
could not be sufficient enough too, therefore, he was
a probable candidate for this kind of tumor.
LSpCC occurs as a result of various
elements, including genetic predisposition,
however, it may also be provoked by a combination
of other conditions, such as injury and inflammation
in patients who are predisposed to this type of tumor
(4). Researchers hypothesized that the development
of the spindle cell phenotype includes a functional
loss of genes controlling epithelial differentiation
and that the reorganization to the spindle
morphology is a recessive entrance (15).
During the pathological evaluation, both
squamous cell and spindle-shaped cell components
should be assessed (5). It is important to mention
that biopsy samples that are taken superficially or in
not big enough pieces, may lead to losing one of the
components of the biphasic tumor, which may
result in misdiagnosis of LSpCC as sarcoma or SCC
(16).
When dealing with tumors of the larynx,
radiologic imaging is necessary to determine the
location of the growth and the invasion level to
surrounding tissues. Usually, a head and neck CT
scan is performed (5,17). However, it should be
noted, that in cases like this, where an organ-
preserving surgery is in consideration, MRI is the
superior imaging method, which allows an accurate
evaluation of the exact location of the tumor, its
invasiveness to nearby tissues and plan the surgical
procedure accordingly.
Both surgery and radiotherapy with
chemotherapy, are acceptable treatment options for
spindle cell carcinomas of the larynx. The fact that
this malignancy is usually superficial and lacks a
well-developed invasion, makes it easy to remove
by various surgical methods (6). As cancer cure,
preservation of larynx function, good voice quality,
low risks of complications, and quality of life have
become the most important goals in laryngeal
cancer treatment, less invasive surgeries with better
functional results are usually chosen (7,18). In this
case, it was possible to treat the patient with radio-
chemotherapy after the success of neo-adjuvant
chemotherapy, however, it was decided to proceed
with transoral laser microsurgery. The main factors,
that led to this decision, were that the exophytic
tumor was arising from a pedicle, which allowed the
Journal of Medical Sciences. May 18, 2020 - Volume 8 | Issue 16. Electronic-ISSN: 2345-0592
117
performance of a relatively less traumatic, function-
preserving surgery, and that surgical treatment
would lead to a fully correct histological diagnosis.
The demand of adjuvant radio- or
chemoradiotherapy of the larynx and the neck
depends on the histopathologic findings: resection
margins and neck nodes’ status, although,
chemotherapy is usually not preferred in this type of
malignancies as they are usually chemoresistant
(18,19) In our patient’s case, neoadjuvant
chemotherapy was prescribed. The decision was
made regarding LSpCC’s low incidence which
decides that no optimal treatment strategies are
available yet and each hospital’s multidisciplinary
tumor-board evaluates the individual case and
concludes the necessity of chemotherapy. Our
patient had a large mass of tumor which needed to
be shrunk before less invasive surgery to achieve
better results.
Other treatment options’, such as
radiotherapy, benefits remain less clear (10).
According to the recent studies in those cases where
radiotherapy was used studies report that patients
achieved 5-year disease-specific survival (DSS) of
75.6%, which did not vary by a margin from cases
for whom radiotherapy was not used (75.8%) (2).
On the other hand, it is noted that the best prognosis
is for patients who were treated using surgery in
combination with radiotherapy (84.2%) because it
provides an effective adjunctive therapy (2,4).
However, this DSS rate is almost the same as in
cases where only surgery was used without
radiotherapy (84.0%) (2). In a discussion about
radiotherapy’s necessity, some authors believe that
radiotherapy should be a compulsory adjunct to
surgery due to surgery alone is not effective enough
(4). If radiotherapy is used as the sole treatment
method, patients have the least favorable outcomes,
however, it is important to mention that these cases
may represent situations when surgery is not
suitable due to the spread of cancer (2).
Radiotherapy is also indicated in those cases when
there is a recurrent tumor or tumor with extensive
stromal invasion (9). However, some studies claim
that the mesenchymal component of LSpCC is
resistant to radiation and as a result, it is not
suggested for this tumor’s treatment (5,7). In our
patient’s case, postoperative radiotherapy was
needed due to the tumor’s poor differentiation
degree and more than 2 positive lymph nodes.
All treatment options have their
disadvantages, however, both chemotherapy and
radiotherapy are associated with serious adverse
effects, such as xerostomia, dysphagia, trismus,
mandibular fibrosis, radionecrosis, and pharyngeal
strictures. Systemic adverse effects include
infections, bone marrow toxicity, renal failure,
neuropathy, nutritional deficiencies, and fatigue
(17,20). Therefore, it is important to consider which
treatment method is the best option for a specific
patient, and when signs of side effects appear, a
physician should reconsider treatment possibilities.
Spindle cell carcinoma of the larynx is
linked with a better outcome in contrast to other
locations in the upper aerodigestive tract (9). The
prognosis is worse in cases where patients have a
high-stage disease, tumors > 3 cm, non-glottic
tumors, fixed vocal folds, radiotherapy in history, in
histological examination necrosis is observed, and
epithelium-positive immunoreactivity (6).
According to the latest studies, the local recurrence
rate is between 16 and 32% (5).
Journal of Medical Sciences. May 18, 2020 - Volume 8 | Issue 16. Electronic-ISSN: 2345-0592
118
In conclusion, LSpCC is an uncommon
occurrence that can be diagnosed only after
histopathological evaluation. A wide local excision
alone in most cases is sufficient enough in the early-
stage disease. Postoperative radiotherapy can be
beneficial if there are other risk factors for
recurrence. An important area for future assessment
would be to resolve the extent and sequence of the
surgery and radiation to achieve optimal survival.
References
1. Virchov R. Die krankhaften Geschweulste.
Berlin, Germany: A. Hirschwald. Online
Resource 1863;
2. Dubal PM, Marchiano E, Kam D, Dutta R,
Kalyoussef E, Baredes S, et al. Laryngeal
spindle cell carcinoma: A population-based
analysis of incidence and survival.
Laryngoscope 2015; 125: 2709–14.
3. Su HH, Chu ST, Hou YY, Chang KP, Chen
CJ. Spindle cell carcinoma of the oral cavity
and oropharynx: Factor affecting outcome.
J Chinese Med Assoc 2006; 69: 478–83.
4. Zheng Y, Xiao M, Tang J.
Clinicopathological and
immunohistochemical analysis of spindle
cell carcinoma of the larynx or
hypopharynx: A report of three cases.
Oncol Lett 2014; 8: 748–52.
5. MG D, D B, S A, K BK. Sarcomatoid
Carcinoma of Larynx: Case report. SAJ
Case Reports 2015; 2: 63–6.
6. Thompson LDR. Laryngeal spindle cell
squamous cell carcinoma. Ear, Nose Throat
J 2011; 90: 214–6.
7. Faisal M, Jamshed A, Hussain R. Spindle
Cell Carcinoma of Larynx- a Distinct
Clinicopathological and Histological
Entity. J Cancer Allied Spec 2017 ; 3: 2–5.
8. Gerry D, Fritsch VA, Lentsch EJ. Spindle
cell carcinoma of the upper aerodigestive
tract: An analysis of 341 cases with
comparison to conventional squamous cell
carcinoma. Ann Otol Rhinol Laryngol
2014; 123: 576–83.
9. Roy S, Purgina B, Seethala RR. Spindle
Cell Carcinoma of the Larynx with
Rhabdomyoblastic Heterologous Element:
A Rare Form of Divergent Differentiation.
Head Neck Pathol 2013; 7: 263–7.
10. Thompson LDR, Wieneke JA, Miettinen
M, Heffner DK. Spindle cell (sarcomatoid)
carcinomas of the larynx: A
clinicopathologic study of 187 cases. Am J
Surg Pathol 2002; 26: 153–70.
11. Miyahara H, Tsuruta Y, Yane K, Ogawa Y.
Spindle cell carcinoma of the larynx. Auris
Nasus Larynx 2004; 31: 177–82.
12. Watson RF, Chernock RD, Wang X, Liu W,
Ma XJ, Luo Y, et al. Spindle Cell
Carcinomas of the Head and Neck Rarely
Harbor Transcriptionally-Active Human
Papillomavirus. Head Neck Pathol 2013; 7:
250–7.
13. Kudo Y, Ogawa I, Kitagawa M, Kitajima S,
Samadarani Siriwardena M, Aobara N, et
al. Establishment and characterization of a
spindle cell squamous carcinoma cell line. J
Oral Pathol Med 2006; 35: 479–83.
14. K HK, Ganesharaja S. Role of
Radiotherapy in Carcinosarcoma Larynx –
A Rare Case Scenario. J Curr Med Res
Opin 2019; 02: 196–8.
Journal of Medical Sciences. May 18, 2020 - Volume 8 | Issue 16. Electronic-ISSN: 2345-0592
119
15. Munakata R, Cheng J, Nakajima T, Saku T.
Spindle cell carcinoma of the gingiva:
report of an autopsy case. J Oral Pathol Med
1998; 27: 180–4.
16. Bostanci A, Ozbilim G, Turhan M. Spindle
Cell Carcinoma of the Larynx: A Confusing
Diagnosis for the Pathologist and Clinician.
Case Rep Otolaryngol 2015; 2015: 1–4.
17. Karatzanis AD, Psychogios G, Waldfahrer
F, Kapsreiter M, Zenk J, Velegrakis GA, et
al. Management of locally advanced
laryngeal cancer. J Otolaryngol - Head
Neck Surg 2014; 43: 1–6.
18. Ambrosch P, Gonzalez-Donate M, Fazel A,
Schmalz C, Hedderich J. Transoral laser
microsurgery for supraglottic cancer. Front
Oncol 2018; 8: 1–10.
19. Divyashree N, John C. Carcinosarcoma
(Spindle Cell Variant) of Larynx–Role of
Radiotherapy 2016; 4: 286–8.
20. Machtay M, Moughan J, Trotti A, Garden
AS, Weber RS, Cooper JS, et al. Factors
associated with severe late toxicity after
concurrent chemoradiation for locally
advanced head and neck cancer: An RTOG
analysis. J Clin Oncol 2008; 26: 3582–9.