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V. F. Kaul et al.
Histology
• Histological hallmark is the deposition of osteoid
• Majority are high-grade lesions
• Osteoblastic, chondroblastic, broblastic, small cell, telangiectatic depending on
the cell type observed
• Chondroblastic osteosarcoma can be difcult to distinguish from chondrosarcoma; immunohistochemical markers such as galectin-1 and ezmin can be used
to distinguish chondroblastic osteosarcoma
Imaging
• CT and MRI to evaluate bone and soft tissue involvement, respectively
• PET/CT useful to rule out metastatic disease
Treatment
• Surgery is the mainstay of treatment; negative margins are critical for improved
outcomes
• Current literature indicates that radiotherapy is controversial and should be
reserved for palliation, or occasionally adjuvant therapy with close or positive margins
• Postoperative chemotherapy
• For nonresectable tumors, proton therapy has offered some local
regional control
• 60–70% overall survival
Chondrosarcoma
Epidemiology
• 10% of malignant bone tumors and are the second most common sarcoma arising
in bone after osteosarcoma
• Predilection for the maxilla and sino-nasal structures
• Can also arise in the petrous temporal bone or in the clivus, and larynx
• Mean age around 30–40
• Head and neck chondrosarcomas tend to be lower grade than other locations
• Recurrence is common and associated with positive margins
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• Most common cause of death is local destruction, metastasis commonly to
the lungs
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Presentation
• Low incidence of regional metastasis of <5%
• Swelling and mild pain, slowly enlarging mass
Histology
• Low-grade chondrosarcomas—few mitotic gures with bland enlarged
chondrocytes
• High-grade chondrosarcomas show hypercellular stroma consisting of characteristic “blue-balls of cartilage” lesion which permeate the trabeculae
• Rare clear cell variant is more aggressive, most common in larynx
• S-100 positive (chondroid origin), SOX9 positive can exclude from other small
round blue cell tumors
Imaging
• CT and MRI to evaluate bone and soft tissue involvement, respectively
• PET/CT useful to rule out metastatic disease
Treatment
• Surgical resection, the mainstay of treatment, with wide excision is required to
achieve clear margins
• Recurrence is common
• If high-grade disease in the larynx, total laryngectomy is recommended
• May have microscopic ngerlike extensions and risk of seeding the wound with
late nodular recurrence
• Radiation plays a palliative role because they are not radiosensitive, with no
improvement in survival benet
• Proton therapy has recently played a central role in therapy for base of skull and
spine lesions
• Chemotherapy plays a limited role in low-grade lesions, but can be used in highgrade lesions
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V. F. Kaul et al.
Radiation-Induced Sarcoma
Epidemiology
• Lesions with different histological features to those of the sarcomas arising in
radiation naïve tissues
• Must meet the following criteria:
– Histological or radiological proof that there was no previous tumor in the
involved area
– Development of sarcoma in an irradiated area
– Sufciently long interval between irradiation and the development of sarcoma
– Histological proof of sarcoma
Presentation
• Occur after previous radiotherapy for benign or malignant disease
• Arise after a median latent period of 9–12years
Histology
• High-grade malignant brous histiocytoma is the most common
• Osteosarcoma second most common
Imaging
• CT and MRI to evaluate bone and soft tissue involvement, respectively
• PET/CT useful to rule out metastatic disease
Treatment
• Prognosis is generally poor but a proportion of these patients can be cured
• 25–30% 5-year survival
• Irradiation is contraindicated and chemotherapy responses are poor
• Surgical resection is the treatment of choice but margins are difcult to ascertain
due to radiation brosis
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Chemotherapy
• 50% of soft tissue sarcoma patients will present with metastatic disease
• Olaratumab is a PDGFR-alpha antibody with a poorly understood mechanism of
action, thought to interact with the tumor stroma thereby increasing delivery of
other systemic therapies
• Recent phase III trials showed no overall survival advantage; therefore, it is currently removed from NCCN guidelines and doxorubicin is the recommended
single agent
• Pazopanib is a tyrosine kinase inhibitor which is an NCCN guideline-approved
drug but now is approved for advanced soft tissue sarcoma who have received
prior chemotherapy.
• Regorafenib is another broad-spectrum tyrosine kinase inhibitor which was
added to NCCN guidelines as second-line therapy for soft tissue sarcomas
Further Reading
1. Mendenhall WM, Fernandes R, Werning JW, Vaysberg M, Malyapa RS, Mendenhall NP.Head
and neck osteosarcoma. Am J Otolaryngol. 2011;32(6):597–600.
2. Nishioka T, Tsuchiya K, Nishioka S, Kitahara T, Ohmori K, Homma A, etal. Pilot study of
modied version of CHOP plus radiotherapy for early-stage aggressive non-Hodgkins lymphoma of the head and neck. Int J Radiat Oncol Biol Phys. 2004;60(3):847–52.
3. AJCC cancer staging manual, 8th ed. Chicago, IL: American Joint Committee on Cancer;
2018. p.1–507.
4. Angouridakis N, Kafas P, Jerjes W, Triaridis S, Upile T, Karkavelas G, et al.
Dermatobrosarcoma protuberans with brosarcomatous transformation of the head and
neck. Head Neck Oncol. 2011;3(1):5.
5. Ashraf MJ, Makarempour A, Monabati A, Azarpira N, Khademi B, Hakimzadeh A, etal.
Comparison between presence of Epstein Barr virus in nodal and extra nodal diffuse
large B cell lymphoma of head and neck, an Iranian experience. Iran Red Crescent Med
J. 2012;14(12):764–70.
6. Beasley M.Lymphoma of the thyroid and head and neck. Clin Oncol. 2012;24(5):345–51.
7. Cabeçadas J, Martinez D, Andreasen S, etal. Lymphomas of the head and neck region: an
update. Virchows Arch. 2019;474(6):649–65.
8. Chi H-S, Lee K-W, Chiang F-Y, Tai C-F, Wang L-F, Yang S-F, etal. Head and neck extranodal lymphoma in a single institute: a 17-year retrospective analysis. Kaohsiung J Med Sci.
2012;28(8):435–41.
9. Chander S, Webster GC, Zingas AP, Zak IT, Joyrich RN, Zerin JM, etal. American Burkittʼs
lymphoma of the head and neck. Clin Nucl Med. 2004;29(10):646–8.
10. Clark DW, Moore BA, Patel SR, Guadagnolo BA, Roberts DB, Sturgis EM.Malignant brous
histiocytoma of the head and neck region. Head Neck. 2011;33(3):303–8.
11. Crist WM, Anderson JR, Meza JL, Fryer C, Raney RB, Ruymann FB, et al. Intergroup
rhabdomyosarcoma study-IV: results for patients with nonmetastatic disease. J Clin Oncol.
2001;19(12):3091–102.
12. Curtis AE, Okcu MF, Chintagumpala M, Teh BS, Paulino AC.Local control after intensitymodulated radiotherapy for head-and-neck rhabdomyosarcoma. Int J Radiat Oncol Biol Phys.
2009;73(1):173–7.
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13. Davis EC, Ballo MT, Luna MA, Patel SR, Roberts DB, Nong X, etal. Liposarcoma of the
head and neck: the University of Texas M.D. Anderson Cancer Center experience. Head Neck.
2009;31(1):28–36.
14. Etemad-Moghadam S, Tirgary F, Keshavarz S, Alaeddini M.Head and neck non- Hodgkins
lymphoma: a 20-year demographic study of 381 cases. Int J Oral Maxillofac Surg.
2010;39(9):869–72.
15. Frisch S, Timmermann B.The evolving role of proton beam therapy for sarcomas. Clin Oncol.
2017;29(8):500–6.
16. Gallamini A, Tarella C, Viviani S, Rossi A, Patti C, Mulé A, etal. Early chemotherapy intensication with escalated BEACOPP in patients with advanced-stage Hodgkin lymphoma with
a positive interim positron emission tomography/computed tomography scan after two ABVD
cycles: long-term results of the GITIL/FIL HD 0607 trial. J Clin Oncol. 2018;36(5):454–62.
17. George S.Developments in systemic therapy for soft tissue and bone sarcomas. J Natl Compr
Cancer Netw. 2019;17(5.5):625–8.
18. Gradoni P, Giordano D, Oretti G, Fantoni M, Barone A, Cava SL, etal. Clinical outcomes
of rhabdomyosarcoma and Ewings sarcoma of the head and neck in children. Auris Nasus
Larynx. 2011;38(4):480–6.
19. Grigore R, Bertesteanu SV, Mogoanta CA.Immunologic and cytogenetic markers expressed in
non-Hodgkin lymphoma of head and neck. Romanian J Morphol Embryol. 2012;53(1):99–104.
20. Hay A, Paii I, Pitkin L, Wilson P, Deery A, Williamson P. Value of ne needle aspiration
cytology in head and neck lymphoma: experience in a head and neck cancer unit in the United
Kingdom. Clin Oncol. 2011;22(10):899.
21. Hoskin PJ, Lowry L, Horwich A, Jack A, Mead B, Hancock BW, etal. Randomized comparison of the Stanford V regimen and ABVD in the treatment of advanced Hodgkins lymphoma:
United Kingdom National Cancer Research Institute Lymphoma Group Study ISRCTN
64141244. J Clin Oncol. 2009;27(32):5390–6.
22. Hsi ED.T-cell lymphoma in the head and neck? Think about adult T-cell leukemia/lymphoma.
Leuk Lymphoma. 2009;50(2):150–1.
23. Hung L-Y, Chang P-H, Lee T-J, Hsu Y-P, Chen Y-W, Fu C-H, etal. Extranodal natural killer/T- cell lymphoma, nasal type: clinical and computed tomography ndings in the head and neck
region. Laryngoscope. 2012;122(12):2632–9.
24. Kim H, Choi N, Baek C-H, Son Y-I, Jeong H-S, Chung MK.Comparison of prognostic implications between the 7th and 8th edition of AJCC TNM staging system for head and neck softtissue sarcoma in adult patients. Eur Arch Otorhinolaryngol. 2019;276(11):3195–202.
25. Koontz BF, Miles EF, Rubio MAD, Madden JF, Fisher SR, Scher RL, et al. Preoperative
radiotherapy and bevacizumab for angiosarcoma of the head and neck: two case studies. Head
Neck. 2008;30(2):262–6.
26. Kusuma S, Skarupa DJ, Ely KA, Cmelak AJ, Burkey BB.Synovial sarcoma of the head and
neck: a review of its diagnosis and management and a report of a rare case of orbital involvement. Ear Nose Throat J. 2010;89(6):280–3.
27. Makimoto Y, Yamamoto S, Takano H, Motoori K, Ueda T, Kazama T, etal. Imaging ndings
of radiation-induced sarcoma of the head and neck. Br J Radiol. 2007;80(958):790–7.
28. Manolopoulos L, Gomatos IP, Leandros E, Alevizos L, Georgiou N, Giotakis J, etal. Use of
rituximab in combination with conventional chemotherapy for the treatment of non-Hodgkin’s
lymphoma of the head and neck. In Vivo. 2009;23(3):475–8.
29. Mendenhall WM, Mendenhall CM, Werning JW, Reith JD, Mendenhall NP.Cutaneous angiosarcoma. Am J Clin Oncol. 2006;29(5):524–8.
30. Miyagi T, Nagasaki A, Taira T, Shinhama A, Suzuki M, Ohshima K, etal. Extranodal adult
T-cell leukemia/lymphoma of the head and neck: a clinicopathological study of nine cases and
a review of the literature. Leuk Lymphoma. 2009;50(2):187–95.
31. Mokhtari S, Mirafsharieh A.Clear cell chondrosarcoma of the head and neck. Head Neck
Oncol. 2012;4(1):13.
32. NCCN guidelines for patients: soft tissue sarcoma. S.l.: NCCN; 2018.
V. F. Kaul et al.
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33. O’Sullivan B, Maki RG, Agulnik M, Patel SG, Lazar AJ, Jones RL, etal. Soft tissue sarcoma
of the head and neck. In: Amin MB, Edge SB, Greene FL, etal., editors. AJCC cancer staging
manual; 2017. p.499–505.
34. Ohba S, Matsumoto F, Fujimaki M, Ito S, Yokoyama J, Ikeda K.Embryonal rhabdomyosarcoma of the head and neck in an adult. Auris Nasus Larynx. 2012;39(3):326–8.
35. Park S-W, Kim H-J, Lee J, Ko Y-H.Malignant brous histiocytoma of the head and neck: CT
and MR imaging ndings. Am J Neuroradiol. 2008;30(1):71–6.
36. Prado FO, Nishimoto IN, Perez DEDC, Kowalski LP, Lopes MA.Head and neck chondrosarcoma: analysis of 16 cases. Br J Oral Maxillofac Surg. 2009;47(7):555–7.
37. Sissolak G, Juritz J, Sissolak D, Wood L, Jacobs P.Lymphoma– emerging realities in subSaharan Africa. Transfus Apher Sci. 2010;42(2):141–50.
38. Tanaka K, Ozaki T.New TNM classication (AJCC eighth edition) of bone and soft tissue sarcomas: JCOG Bone and Soft Tissue Tumor Study Group. Jpn J Clin Oncol. 2018;49(2):103–7.
39. Tudor-Green B, Gomez R, Brennan PA.Current update on the diagnosis and management of
head and neck soft tissue sarcomas. J Oral Pathol Med. 2017;46(9):674–9.
40. Turner JH, Richmon JD.Head and neck rhabdomyosarcoma: a critical analysis of populationbased incidence and survival data. Otolaryngol Head Neck Surg. 2011;145(6):967–73.
41. Zapater E, Bagán J, Carbonell F, Basterra J.Malignant lymphoma of the head and neck. Oral
Dis. 2010;16(2):119–28.
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Chapter 20
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Laryngeal Squamous Cell Carcinoma
ArvindK.Badhey, VictorJ.Schorn, BrettA.Miles, andMohemmedKhan
Pearls
• Early-stage laryngeal SCC can be treated surgically via a variety of transoral
techniques or nonsurgically with RT; both have excellent oncologic outcomes.
• Transoral surgical techniques have improved swallowing outcomes but slightly
worse voice quality when compared to RT for early disease.
• Glottic SCC rarely exhibits cervical metastasis, unless disease is advanced.
• Supraglottic SCC often exhibits cervical metastasis and has a poor prognosis
compared to laryngeal SCC.
• Laryngectomy is typically reserved for advanced tumors, salvage therapy, or
recurrence. Chondrosarcoma of the larynx most commonly involves the cricoid,
in which surgery is the primary treatment modality.
A. K. Badhey (*)
Department of Otolaryngology, UMass Memorial Medical Center, University of
Massachusetts Medical School, Worcester, MA, USA
V. J. Schorn
Head and Neck Surgery, Kaiser Permanente– West Los Angeles, Los Angeles, CA, USA
e-mail: Victor.j.schorn@kp.org
B. A. Miles
Otolaryngology Head and Neck Surgery, Oral and Maxillofacial Surgery, Northwell Health
System, New Hyde Park, NY, USA
e-mail: bmiles4@northwell.edu
M. Khan
Department of Otolaryngology - Head and Neck Surgery, Icahn School of Medicine at the
Mount Sinai Hospital, New York, NY, USA
e-mail: mohemmed.khan@mountsinai.org
© Springer Nature Switzerland AG 2023
F. Y. Lin, Z. M. Patel (eds.), ENT Board Prep,
https://doi.org/10.1007/978-3-031-26048-3_20
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A. K. Badhey et al.
Anatomy
• Supraglottis
– Suprahyoid/Infrahyoid Epiglottis, aryepiglottic folds, arytenoids, false
vocal cords.
– Bilateral lymphatic drainage, levels II, III, IV.
Tendency for early lymphatic metastasis.
• T1—10%
• T2—29%
• T3—38%
• T4—57%
– Predominantly pseudostratied columnar epithelium.
– Derived from third to fourth branchial arches.
• Glottis
– True vocal cords, including the anterior and posterior commissures.
– Stratied squamous epithelium.
– Unilateral lymphatic drainage, levels II, III, IV, and VI.
– Involvement of anterior commissure increases risk of cervical metastasis due
to spread along Broyle’s ligament
Infrequent lymphatic metastasis.
• T1—0.1%
• T2—5%
• T3—18%
• T4—32%
– Derived from sixth branchial arch.
• Subglottis
– Lower border of glottis to inferior border of cricoid cartilage.
– Pseudostratied columnar epithelium.
– Paratracheal nodes most common site of regional metastases.
– Derived from sixth branchial arch.
• Pre-epiglottic space (PES)
– Potential for spread through fenestrations in the epiglottis
– Involvement upstages lesions to T3
– Superior boundaries.
Hyoepiglottic ligament.
Vallecula.
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– Anterior
Thyrohyoid ligament.
Thyroid cartilage.
Hyoid.
– Posterior
Epiglottis.
Thyroepiglottic ligament.
• Paraglottic space (PGS)
– Provides route of vertical spread, continuous with PES.
– Involvement upstages to T3
– Lateral boundaries.
Thyroid cartilage.
Pyriform sinus.
Cricothyroid membrane.
– Medial boundaries
Quadrangular membrane superiorly.
Laryngeal ventricle.
Conus elasticus inferiorly.
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Epidemiology
• SCCA accounts for 85–95% of laryngeal CA.
• Male to female 3.8:1 due to increased exposure to risk factors.
• Peak in sixth and seventh decades of life.
• Tobacco, alcohol usage main environmental causes, synergistic.
– Tobacco more commonly associated with glottic SCCA.
– Alcohol more commonly associated with supraglottic SCCA.
• Laryngopharyngeal reux moderately increases risk.
• Glottic SCCA slightly more common than supraglottic SCCA in the United States.
• Subglottic rare, 1% of laryngeal SCC.
• Presentation dependent on site.
– Supraglottic SCCA commonly presents in advanced stage with neck disease.
Dysphonia, dysphagia, odynophagia, otalgia, dyspnea, stridor.
– Glottic SCCA more commonly presents at early stage.
Dysphonia, dyspnea, stridor.
– Subglottic SCCA often presents at late stage, with frequent distant metastases.
Dyspnea, stridor.
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Work-Up andStaging
• Complete head and neck history and physical.
– Particular attention to risk factor exposure.
– Comorbidities, particularly COPD, and lung disease.
• Fiber-optic laryngoscopic examination, with particular attention to vocal fold
mobility.
• Imaging
– CT with contrast or MRI of head and neck.
– Important to assess invasion of the pre-epiglottic space, paraglottic space,
laryngeal cartilages.
– PET/CT to assess for regional and distant metastases, and synchronous
primary.
– Chest CT or chest radiograph, given frequency of synchronous primary lung
CA and lung metastases.
• Labs
– Standard preoperative labs, with particular attention to nutritional status.
• Direct laryngoscopy with biopsy.
– Palpation of vocal folds.
– Use of angled endoscopes to evaluate ventricles, underside of vocal cords.
– Signicant airway compromise may require awake tracheostomy under local
anesthesia prior to laryngoscopy.
• Tracheostomy should be done as high as possible to preserve trachea if future
laryngectomy is suspected. Pulmonary function tests indicated in case of partial
laryngectomy surgery.
TNM Staging asper AJCC
Primary tumor (T): Supraglottis
• TX—Primary tumor cannot be assessed
• T0—No evidence of primary tumor
• Tis—Carcinoma in situ
• T1—Tumor limited to one subsite of supraglottis with normal vocal cord
mobility
• T2—Tumor involving more than adjacent subsite of supraglottis or glottis or
region outside supraglottis (base of tongue, vallecula, medial wall pyriform
sinus), without xation of larynx
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