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Tonsil carcinoma

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Tonsil carcinoma
SpecialtyOncology

Carcinoma of the tonsil is a type of squamous cell carcinoma. The tonsil is the most common site of squamous cell carcinoma in the oropharynx. It comprises 23.1% of all malignancies of the oropharynx.[1] The tumors frequently present at advanced stages, and around 70% of patients present with metastasis to the cervical lymph nodes.[2] . The most reported complaints include sore throat, otalgia or dysphagia. Some patients may complain of feeling the presence of a lump in the throat. Approximately 20% patients present with a node in the neck as the only symptom.[3]

Main risk factors of developing carcinoma tonsil include tobacco smoking and regular intake of high amount of alcohol. It has also been linked to human papilloma virus (HPV type HPV16).[4] Other risk factors include poor maintenance of oral hygiene, a genetic predisposition leading to inclination towards development of throat cancer, immunocompromised states (such as post solid-organ transplant), and chronic exposure to agents such as asbestos and perchloroethylene in certain occupations, radiation therapy and dietary factors.[5]

Signs and symptoms

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The early lesions are usually asymptomatic. The patients presenting with an advanced stage of the disease comprises around 66–77% of the cases.[6]

The most important signs include a lump in the neck when palpated and weight loss.[7] People may also present with fatigue as a symptom.[citation needed]

The primary tumor does not have readily discernible signs or symptoms as they grow within the tonsillar capsule. It is difficult to notice anything suspicious on examination of the tonsil other than slight enlargement or the development of firmness around the area. The carcinoma may occur in one or more sites deep within the tonsillar crypts. It may be accompanied by the enlargement of the tonsil. The affected tonsil grows into the oropharyngeal space making it noticeable by the patient in the form of a neck mass mostly in the jugulodigastric region. As the tonsils consist of a rich network of lymphatics, the carcinoma may metastasize to the neck lymph nodes which many are cystic. Extension of tumor to skull or mediastinum can occur.

The additional symptoms include a painful throat, dysphagia, otalgia (due to cranial nerve involvement), foreign body sensation, bleeding, fixation of tongue (infiltration of deep muscles) and trismus (if the pterygoid muscle is involved in the parapharyngeal space).[citation needed]

On the other hand, the tumor may also present as a deep red or white fungating wound growing outwards, breaking the skin surface with a central ulceration. This wound-like ulcer fails to heal (non-healing) leading to bleeding and throat pain and other associated symptoms.[citation needed]

During biopsy, the lesion may show three signs: gritty texture, firmness and cystification owing to keratinization, fibrosis and necrosis respectively.[8]

Cervical lymphadenopathy may be present.[citation needed]

Cause

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Smoking and alcohol abuse are the major risk factors.[9] Viral causes have recently been taken under consideration as one of the risk factors. Viruses such as Epstein-Barr virus (EBV) (majorly involved in causing nasopharyngeal carcinoma) and human papilloma virus are included in this category. Chewing of betel nut (Areca catechu) quid has been directly associated to cause oral cancers.[10] It has also been stated under the FDA poisonous plant data base by the U.S Food and Drug Administration [11] An unbalanced diet, deficit in fruits and vegetables has shown to increase the risk of cancer.[12]

Pathophysiology

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Direction of spread Structures involved
Along Glossotonsillar sulcus Base of tongue
Superior Soft palate or nasopharynx
Laterally (Infiltrating through the constrictor muscle) Pharyngeal space, Pterygoid musculature, Mandible
Superior spread through parapharyngeal space Base of skull
Inferior Lateral neck
Extensive spread in parapharyngeal space Carotid artery, Carotid sheath

Metastasis to regional lymphnodes is common as the tonsil has a rich supply of lymphatics giving way to the tumor cells to metastasis to other lymph nodes (commonly the lymph nodes of neck) and cause lymphydenopathy. The cervical lyphydenopathy can be ipsilateral (70% or more patients) or bilateral (30% and fewer patients).[13] The carcinoma of tonsil usually spreads through the cervical lymph node levels II, III, IV, V, and retropharyngeal lymph nodes.[citation needed]

The fourth edition of WHO' s classification of head and neck tumors subdivides squamous cell carcinoma of the tonsil into two types: HPV positive or negative. HPV positive tumors arise from the deep lymphoid tissue of the tonsillar crypts and are non-keratinizing. On the other hand HPV negative tumors develop from the tonsillar surface epithelium and hence have keratinizing dysplasia.[14]

Routes of metastasis

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Metastasis is common in tonsillar carcinoma. It largely depends on the stage of the cancer and the route through with the cancer cells metastasize. The cancer cells may spread to adjacent structures, to lymphatics or to distant locations in the body producing secondary tumors.[citation needed]

Local

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The tumor may spread locally to soft palate and pillars, base of tongue, pharyngeal wall and hypopharynx. It may invade pterygoid muscles and mandible, resulting in pain and trismus. Parapharyngeal space may also get invaded.[15]

Lymphatic

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50% of patients have initial cervical node involvement at the time of presentation. Jugulodigastric lymph nodes are the first to be involved.[15]

Distant metastasis

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The occurrence of distant metastasis varies extensively, ranging between 4–31% in clinical studies. Factors influencing the incidence of distant metastasis are:[citation needed]

  • Location of primary tumor
  • Initial staging
  • Histological differentiation
  • Loco-regional control of the primary tumor

The records of 471 male patients with tonsillar carcinoma seen at the Veterans Administration Medical Center, Hines, Illinois, have been reviewed to establish the incidence and site of distant metastasis. All the patients were histological diagnosed and proven cases of tonsillar carcinoma. 72 (15%) out of 471 patients and 33 (29%) of 155 autopsied patients were reported to have distant metastasis.

Squamous cell carcinoma was the most common reported cell type (88%); cases with lymphoepithelioma had the highest incidence of distant metastasis.[16] The most common anatomical sites of incidence of distant metastasis include lung, liver and bones. Thorough investigation of these organs is highly recommended before treatment as well as during follow-ups.[citation needed]

Diagnosis

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The first step to diagnosing tonsil carcinoma is to obtain an accurate history from the patient. The physician will also examine the patient for any indicative physical signs. A few tests then, maybe conducted depending on the progress of the disease or if the doctor feels the need for.[citation needed] The tests include: Fine needle aspiration, blood tests, MRI, x-rays and PET scan.

Staging

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The staging of a tumor mass is based on TNM staging.[17]

T staging is the based on the tumor mass. The N staging is based on the extent of spread of cancer to the lymph nodes. Finally, the M stage indicates if the cancer has spread beyond the head and neck or not.[citation needed]

T Staging

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The basis of deciding the T stage depends on physical examination and imaging of the tumor.[citation needed]

T Stage Tumor Dimension
Tx Primary tumor cannot be assessed
T0 Primary tumor cannot be located
Tis Carcinoma in situ
T1 ≤ 2 cm in dimension
T2 > 2 cm but ≤ 4 cm in dimension
T3 > 4 cm and has grown till the epiglottis
T4a Moderately advanced, tumor has grown into larynx, beyond muscles of tongue, hard palate, lower jawbone and/or medial pterygoid muscles
T4b Extremely advanced, invasion of lateral pterygoid muscle, pterygoid plates, nasopharynx, into skull base or is encasing the carotid artery.

N staging

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This stage is decided through the assessment of the lymph nodes.[citation needed]

N Stage Lymph node dimension
Nx No assessment of neck lymph nodes
N0 No evidence of spread
N1 Ipsilateral, Single lymph node, ≤ 3 cm in size
N2a cancer cells have metastasised to a single lymph node, ipsilateral to main tumor, > 3 cm but ≤ 6 cm in size
N2b Cancer cells have metastasised to multiple lymph nodes, ipsilateral to mail tumor, > 6 cm in size
N2c Detection of lymph nodes in the neck, contralateral or bilateral to the main tumor, >6 cm in size
N3 Metastasis of cancer cells to one or more lymph nodes, >6 cm in size

M staging

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Based on the examination of the entire body.

M Stage Metastasis beyond Head and neck
M0 No evidence
M1 Evidence of metastasis to structures outside head and neck present, commonly involved organs are: Lungs, bones, brain

Finally, the stage is decided by concluding the above results and referring the following chart:

Stage T Stage N Stage M Stage
Stage I T1 N0 M0
Stage II T2 N0 M0
Stage III T3 N0 M0
T1 N1 M0
T2 N1 M0
T3 N1 M0
Stage IVA T4a N0 M0
T4a N1 M0
T1 N2 M0
T2 N2 M0
T3 N2 M0
T4a N2 M0
Stage IVB T4b Any N M0
Any T N3 M0
Stage IVC Any T Any N M1

Treatment

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The treatment for tonsil carcinoma includes the following methods:[18][19]

Radiotherapy

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Early radio-sensitive tumors are treated by radiotherapy along with irradiation of cervical nodes. The radiation uses high-energy X-rays, electron beams, or radioactive isotopes to destroy cancer cells.[citation needed]

Chemotherapy

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Induction chemotherapy is the treatment adapted for shrinking the tonsil tumor. It is given prior to other treatments, hence, the term induction. After the therapy is completed, the patient is asked to rest and is evaluated over a period of time. Then the patient is given chemo-radiation therapy (a combination of chemotherapy and radiation) to completely destroy the tumor cells.[20]

Surgery

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If radiation and chemotherapy are unable to destroy the tumor, surgical intervention is considered.[19] Excision of the tonsil can be done for early superficial lesions. Large lesions and those which invade bone require wide surgical excision with hemimandibulectomy and neck dissection (Commando operation)[15]

Combination therapy

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Surgery may be combined with pre- or post operative radiation. Chemotherapy may be given as an adjunct to surgery or radiation.[citation needed]

Prognosis

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Prognosis is determined by various factors such as stage, Human Papilloma Virus (HPV) status, Lymph infiltration of cancer cells, spread of cancer cells beyond the lymph node capsule, margins of the tumor and the extent of metastasis. Many factors are unique to each individual patient and may affect the chances of success of the treatment.

Factors determining the prognosis of tonsillar carcinoma are as follows:[21]

HPV status

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Tonsillar carcinoma can be either HPV related or HPV unrelated. It is shown that cases which are HPV positive have a better prognosis than those with HPV negative oropharyngeal cancer.[citation needed]

Stage

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The stage at which the cancer presents itself affects the type of definitive treatment, chance of cure, recurrence of cancer and survival rate of the patient. Generally the patient presents very late due to the lack of definitive symptoms in the early stages of the disease. Nearly three fourths of the patients present in Stage III or later.[22]

The stages of oropharyngeal cancer are as follows:[23]Stage 0 (carcinoma in situ): This stage indicates a good prognosis as most patients with stage 0 survive for a long period without the requirement of an intensive treatment. Although, the patient must cease smoking as it can increase the risk of developing a new cancer.[citation needed]

Stage I and II: Most patients presenting at this stage receive successful treatment, showing a good prognosis. The modes of treatment for this stage include chemotherapy, surgery, radiation therapy or chemoradiation. The main treatment at this stage is radiation, targeting the tumor and the cervical lymph nodes. Surgical removal of the tumor and lymphadenectomy of the cervical (neck) lymph nodes can also be taken up at the main treatment method instead of radiation. And remaining cancer cells post surgery are treated with chemoradiation.[citation needed]

Stage III and IVA: In this stage the cancer cells metastasize into the local tissues and cervical lymph nodes. The treatment used in these cases is chemo radiation. Any remaining cancer cells post chemoradiation are surgically removed. Lymphadenectomy may also be done after treatment with chemoradiation if the cancer cells have infiltrated the cervical lymph nodes. Another method of treatment includes, first, surgical removal of tumor as well as cervical lymph nodes followed by chemoradiation or radiation to decrease the chances of recurrence.[citation needed]

Stage IVB: In this stage the cancer has already undergone distant metastasis, hence showing poor prognosis. The treatment includes chemotherapy, cetuximab or both. Radiation may be used to aid in relieving symptoms arising from the cancer and also to prevent further development of complications.

Lymphatic infiltration

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Nearly half of the patients with anterior pillar lesions and three fourths of the patients with tonsillar fossa lesions have nodal metastasis at the time of presentation itself.[22] Metastasis of cancer cells to cervical lymph nodes diminishes the chance of cure. Specially, if there is evidence of metastasis of cancer cells beyond the lymph node capsule. Though, some data indicates that the metastasis of cancer cells outside the lymph node capsule is a bad prognosis for HPV-unrelated oropharynx cancer than it is for HPV-related oropharynx.[citation needed]

Tumor extension

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Extension of the tumor to the base of tongue reduces the chances of cure drastically. It also increases the chances of recurrence after treatment.[22]

Metastasis

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Spread of cancer cells to local structures like tissues, vessels, large nerves and lymphatics worsens a patient's prognosis.[citation needed]

A study that analyzed the survival rate in HPV-related oropharynx carcinoma to that in HPV-unrelated oropharynx carcinoma. The study revealed that based on the HPV status of the patient, for STAGE III and STAGE IV oropharynx carcinoma, there was a discrepancy in survival after three years. The survival was 82% in HPV positive and then also 57% in HPV negative cancers.[citation needed]

References

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  1. ^ Williamson, Andrew J. (Jan 13, 2019). "Tonsil Cancer". Cancer, Tonsil. StatPearls. PMID 30725923. {{cite book}}: |website= ignored (help)
  2. ^ Seiden, Allen M.; Tami, Thomas A.; Pensak, Myles L.; Cotton, Robin T.; Gluckman, Jack L. Otolaryngology: The Essentials (2002 ed.). Theime Medical Publishers. p. 194.
  3. ^ Hodder, Arnold (2006). Logan Turner's Diseases of the Nose, Throat and Ear (10th ed.). JAYPEE. p. 113. ISBN 978-93-5025-943-6.
  4. ^ "Tonsil cancer". Cancer Research UK. 2014-08-05. Retrieved 2016-07-16.
  5. ^ "Throat cancer (Squamous Cell Carcinoma of the Tonsil)". MyVMC.com. 2003-01-08. Retrieved 2016-07-16.
  6. ^ Mankekar, G. (2000). "Tonsillar carcinoma- a review" (PDF). Indian J Otolaryngol Head Neck Surg. 52 (3): 310. doi:10.1007/BF03006216. PMC 3451114. PMID 23119708. Archived from the original (PDF) on 17 May 2017. Retrieved 25 September 2016.
  7. ^ "A Non-Profit Hospital in Los Angeles".
  8. ^ "Malignant Tonsil Tumor Surgery". Medscape. Niels Kokot, MD Assistant Professor, Residency Program Director, Department of Otolaryngology–Head and Neck Surgery, Keck School of Medicine of the University of Southern California. Retrieved 25 September 2016.
  9. ^ "Malignant Tonsil Tumor Surgery". Medscape. Niels Kokot, MD Assistant Professor, Residency Program Director, Department of Otolaryngology–Head and Neck Surgery, Keck School of Medicine of the University of Southern California. Retrieved 25 September 2016.
  10. ^ Warnakulasuriya, Saman; Trivedy, Chetan; Peters, Timothy J (5 April 2002). "Areca nut use: an independent risk factor for oral cancer". BMJ. 324 (7341): 799–800. doi:10.1136/bmj.324.7341.799. PMC 1122751. PMID 11934759.
  11. ^ "Second report of the expert advisory committee on herbs and botanical preparations". FDA. Archived from the original on 15 February 2020. Retrieved 26 September 2016.
  12. ^ Key, T J (3 January 2011). "Fruit and vegetables and cancer risk". British Journal of Cancer. 104 (1): 6–11. doi:10.1038/sj.bjc.6606032. PMC 3039795. PMID 21119663.
  13. ^ "Oropharyngeal Cancer Treatment (PDQ®)–Health Professional Version". National Cancer Institute. 1980-01-01. Retrieved 25 September 2016.
  14. ^ Westra, William H.; Lewis, James S. (2017-02-28). "Update from the 4th Edition of the World Health Organization Classification of Head and Neck Tumours: Oropharynx". Head and Neck Pathology. 11 (1): 41–47. doi:10.1007/s12105-017-0793-2. ISSN 1936-055X. PMC 5340734. PMID 28247229.
  15. ^ a b c Dhingra (2013-10-01). Diseases of Ear, Nose and Throat and Neck Surgeries (6th ed.). Elsiver. p. 271. ISBN 978-81-312-3431-0.
  16. ^ Chung TS, Stefani S (1980). "Distant metastases of carcinoma of tonsillar region: a study of 475 patients". Journal of Surgical Oncology. 14 (1): 5–9. doi:10.1002/jso.2930140103. PMID 7382512. S2CID 26204372.
  17. ^ "Determining the Stage of the Cancer". Head and Neck Cancer Guide. Retrieved 25 September 2016.
  18. ^ Dhingra, PL (2014). Diseases of Ear, Nose and Throat & Head and Neck Surgeries (6th ed.). Elsiver. ISBN 978-81-312-3431-0.
  19. ^ a b "Tonsil Cancer".
  20. ^ Vokes EE (2010). "Induction chemotherapy for head and neck cancer: recent data". The Oncologist. 15 (Suppl 3): 3–7. doi:10.1634/theoncologist.2010-S3-03. PMID 21036882. S2CID 5563351.
  21. ^ "Tonsil cancer". Head And Neck Cancer guide. 6 December 2019.
  22. ^ a b c Mankekar, G. (January 2002). "Tonsillar carcinoma: A review". Indian Journal of Otolaryngology and Head and Neck Surgery. 54 (1): 67. doi:10.1007/BF02911013. ISSN 2231-3796. PMC 3450683. PMID 23119859.
  23. ^ "Treatment options for oral cavity and oropharyngeal cancer by stage". The American Cancer Society.