BENIGN AND MALIGNANT NEOPLASIA OF URT

Dr. Sunil

LECTURE OUTCOMES
Describe the pathogenesis, gross and microscopic appearances of benign and malignant neoplasia of the upper respiratory tract. Clinical features, complications of benign and malignant neoplasia of the upper respiratory tract

RESPIRATORY TRACT DIVISION

Paranasal sinuses are air filled spaces lined by respiratory mucosa, located within skull bones.

NASAL POLYPS

NASAL POLYPS
Abnormal polypoid structures/lesions Arise from the nasal mucosa or paranasal sinuses

Left anterior nasal cavity showing an antro-coanal polyp. Inferior turbinate is being pushed to one side!

HISTOLOGY OF NASAL POLYPS

This is an image of a nasal polyp showing the lining respiratory epithelium. The boxes show the (1) normal epithelium, (2) the thin collagenous portion of the polyp and the (3) edematous area which would take up most of the polyp. The presence of eosinophils in the polyp is characteristic

ETIOLOGY AND PATHOGENESIS

Unknown Chronic inflammation Autonomic nervous system dysfunction Genetic predisposition Allergic versus non-allergic

Most theories consider polyps to be the ultimate manifestation of chronic inflammation; therefore, conditions leading to chronic inflammation in the nasal cavity can lead to nasal polyps

THE FOLLOWING CONDITIONS

ASSOCIATED WITH MULTIPLE BENIGN POLYPS

Bronchial asthma - In 20-50% of patients with polyps Cystic Fibrosis (CF) - Polyps in 6-48% of patients with CF Allergic rhinitis Chronic rhinosinusitis Primary ciliary dyskinesia Aspirin intolerance - In 8-26% of patients with polyps Alcohol intolerance - In 50% of patients with nasal polyps Churg-Strauss syndrome - Nasal polyps in 50% of patients with Churg-Strauss syndrome Young syndrome (i.e., chronic sinusitis, nasal polyposis, azoospermia) Non-allergic rhinitis with eosinophilia syndrome (NARES) - Nasal polyps in 20% of patients with NARES

THEORIES FOR DEVELOPMENT OF NASAL

POLYPS
inflammatory changes first occur in the lateral nasal wall or sinus mucosa as the result of viral-bacterial host interactions or secondary to turbulent airflow

Bernsteins theory

Vasomotor theory

vasomotor imbalance theory postulates that increased vascular permeability and impaired vascular regulation cause detoxification of mast-cell products (eg. histamine)

Epithelial rupture theory

The epithelial rupture theory suggests that rupture of the epithelium of the nasal mucosa is caused by increased tissue turgor in illness (eg. allergies, infections). This rupture leads to prolapse of the lamina propria mucosa, forming polyps.

CLINICAL PRESENTATION
Asymptomatic Airway obstruction Postnasal drip Dull headaches Snoring Rhinorrhoea Hyposmia / Anosmia Epistaxis (often other lesion) Obstructive sleep apnoea Craniofacial abnormalities Optic nerve compression

rhinosporidiosis

Allergic fungal sinusitis

Mucormycosis rhinocerebral (diabetes)

PAPILLOMA
Papilloma Occurs in nose, sinuses, larynx (occasionally also in lower airways Associated with human papilloma virus types 6 and 11 Laryngeal lesions commoner in children can occlude airway Three types- Septal, Inverted and Cylindrical

Schneiderian or sinonasal papillomas Benign tumours Arise from sinonasal mucosa Composed of squamous/columnar epithelium HPV types 6 and 11 implicated 3 types - Fungiform - Cylindrical - Inverted (endophytic and biologically important)
If incompletely excised, it recurs several times and with such recurrences chances of local invasion into the orbit or cranial vault are reported! Rarely a frank carcinoma can occur.

Nasal polypoid masses

Nasopharyngeal angiofibroma

Adolescent males/androgen dependent Benign Bleeds during surgery

Nasopharyngeal carcinoma

D/Ds of nasal polypoid tumours

Olfactory neuroblastoma

Lymphoma (Non-Hodgkins)

Angio-centric NK- T cell type

OLFACTORY NEUROBLASTOMA /
ESTHRIONEUROBLASTOMA Uncommon Small, blue, round cell tumour

Resembles neuroblasts proliferating into lobular nests Arises from neuroendocrine cells Aggressive Requires surgery, radiotherapy and chemotherapy 5 year survival rates between 50 to 70%

NPC
Great geographical variation in incidence Asia (Far East) Africa Sporadically elsewhere Associated with EBV infection

Nasopharyngeal carcinomalymphoepithelioma-like carcinoma, lymphoepithelioma, Regauds Type lymphoepithelioma, Schminckes type lymphoepithelioma,

Nasopharyngeal carcinoma in a 62-year-old patient. (a) Coronal PET scan shows intense FDG uptake (arrow) in proximity to the brain. Malignant epithelial tumor arising in the nasopharyngeal mucosa, that includes keratinizing squamous cell carcinoma and nonkeratinizing squamous cell carcinoma (differentiated and undifferentiated) with abundant non-neoplastic, lymphocytic infiltrate.

NASOPHARANGEAL CARCINOMA
Strong epidemiological and biological association with Epstein-Barr virus (detectable in tumour) Other factors diet,smoking Ageincidence curve bimodal: peaks 1525 years and 6069 years Sometimes familial aggregation Present with neck node enlargement and/or nasal symptoms Distant metastases to bone, liver and lungs

PATHOGENESIS
Evidence strongly suggests combined action of: genetic predisposition environmental factors EpsteinBarr virus (EBV):1115 + within tumor EBV DNA is homogeneous andclonal + expression of specific viral messenger RNAs or gene products consistently detected + EBV in tumor tissue (Immunohistochemical demonstration of EBER in nasopharyngeal undifferentiated carcinoma)

Proposed that: o tumor initiation requires EBV expression

CT SCAN

EXAMINATION AND INVESTIGATIONS

Posterior rhinoscopy: The predilection site is the anterior top of the nasopharynx and the pharyngeal recess. Cervical palpation: enlarged lymph nodes Nasopharyngo-scope or nasoendoscopy Serological examination of EB virus: EB VCAIgA, EB NA-IgA(nuclear antigen) Imaging: CT,MRI Biopsy of the nasopharynx

Random blind biopsies taken from nasopharyngeal area should be taken whenever diagnosis is suspected particulary from fossa of Rossenmuller.

HISTOPATHOLOGY Undifferentiated Differentiated (squamous cell) No prognostic difference Tumour frequently has a dense lymphocytic infiltrate (it is sometimes known as lymphoepithelioma)

Immunohistochemical demonstration of EBER in nasopharyngeal non-differentiated carcinoma

ANGIOCENTRIC NK/T CELL TYPE

LYMPHOMA Lethal midline granuloma/midline malignant reticulosis 3% of NHLs in Asia Destructive midline mass involving Nasopharynx Less commonly, involves Skin or extranodal sites such as Testis Contain EBV episomes

MICROSCOPY
Tumour cell infiltrate typically surrounds and invades small vessels, leading to extensive ischaemic necrosis. Mixture of small and large lymphoid cells or predominantly large lymphoid cells. Cytoplasm of tumour cells contain large azurophilic granules

COURSE AND TREATMENT

Indolent course Most are aggressive Poorly responsive to therapy

The larynx is an air passage, an organ of phonation and a sphincteric mechanism between the laryngopharynx and trachea

VOCAL CORDS POLYPS

Benign non-neoplastic nodules in smokers and those putting strain on vocal cords singers nodules

Symptom: Hoarseness or voice change Finding: Nodule: bilateral opposing knotoccurring at mid-vocal cord Polyp: erythematous, smooth, mobile vocal cord lesion larger than nodules, but similar location

They are nonneoplastic lesions of the vocal cords vocal cord nodules/Singers nodules and vocal cord polyps

HISTOLOGY OF VOCAL CORD

POLYPS
Vocal cord nodule/polyp, also known as singers nodules, is a non-neoplastic lesion secondary to inflammation or trauma to the true vocal cord. There are four histologic subtypes: edematous-myxoid, fibrous, vascular, and hyaline. However, most polyps show overlap of these features as seen in the photomicrograph, which demonstrate vascular-hyaline as well as edematous-myxoid composition

TREATMENT

Strict voice rest No whispering (causes as much strain as yelling) Surgical excision under suspension laryngoscope and biopsy.

LARYNGEAL/RECURRENT RESPIRATORY PAPILOMATOSIS (RRP)

Recurrent respiratory papillomatosis (RRP) is a disease caused by the human papillomavirus (HPV). Warty growths in the upper airway may cause significant airway obstruction or voice change RRP has a bimodal age distribution and manifests most commonly in children younger than 5 years (juvenile-onset RRP [JORRP]) or in persons in the fourth decade of life (adult-onset RRP [AORRP]).

ETIOLOGY HPV, the virus associated with cutaneous warts, genital condyloma, and cervical cancer, causes RRP. While more than 20 types of HPV can cause genital warts, only 2 of these, HPV-6 and HPV11, cause the vast majority of cases of RRP. The disease associated with HPV-11 is more severe

CLINICAL PRESENTATION
Hoarseness is the most common presenting symptom. Other symptoms include the following:

* Voice change * Choking episodes * Foreign body sensation in the throat * Cough * Dyspnea * Inspiratory wheeze * Stridor

PATHOLOGY Under low power, the lesion has a papillary appearance. This results from the exophytic growth of keratinized squamous epithelium overlying a fibrovascular core. Koilocytes, vacuolated cells with clear cytoplasmic inclusions, are noted and are indicative of viral infection. Metaplasia and dysplasia occur in varying degrees

LARYNX CARCINOMA
Squamous cell carcinomas comprise 95-98% of all malignant neoplasms of the larynx. Approximately 90% carcinoma of larynx occur in men, with peak incidence between the ages of 55 to 65.

ETIOLOGY

Smoking Alcohol abuse Air pollution Viral infection :HPV16,18 (5%) Precancerous lesion: leukoplakia Exposure to asbestos, irradiation Nutritional factors

LARYNGEAL CARCINOMA

98% squamous cell carcinoma Carcinoma in situ Invasive carcinoma (6 9%) ( 90%) Supraglottic Glottic Infraglottic (30%) (60%) (6%) Intrinsic Confined to larynx proper Extrinsic- arise or extend outside larynx

Supraglottic Glottic portion Infraglottic

LARYNGEAL CARCINOMA
Effects by local tissue destruction (loss of voice/hoarseness) Pain, dysphagia, haemoptysis Secondary infection of the ulcerating lesion Neck node metastases

HISTOPATHOLOGY OF LARYNGEAL
CARCINOMA

Squamous cell carcinoma of the Larynx

BEHAVIOUR

Spreads to lymph nodes Very sensitive to radiotherapy

TREATMENT Surgery, radiation or combination therapy 1/3rd die of the disease Usual cause of death- Infection of distal respiratory passages or wide-spread metastases and cachexia.