Larynx, Trachea, Lung and Pleura

Celso S. Ramos, MD, FPSP, MBA-H

Larynx
 Supraglottic portion derived from the 3rd
and 4th pharyngeal pouches
 Glottis and subglottis – originate from the
6th branchial pouch
 Epiglottis
◦ Lingual – anterior surface - SS Epithelium
◦ Laryngeal- posterior- SSE and resp epith
 Larynx
◦ Supra glottic and intraglottic – resp epithelium
◦ Glottis – SS Epithelium
Larynx
 Laryngeal nodule- noninflammatory reaction
causing hoarseness
◦ Seen at the anterior 3rd of the vocal cord
◦ Those who misuse their voice – singer’s nodule
 Contact ulcer – granulomatous ulcer
frequently seen in the posterior commissure
◦ Exuberant granulation tissue- similar to pyogenic
granuloma
◦ Conservative management
Laryngeal nodule
Larynx
 Papilloma and papillomatosis
◦ Juvenile – children and adolescents- HPV
associated – HPV 6 and 11
◦ Recurring lesion and maybe over-diagnosed as
Carcinoma
◦ Rarely it may develop to squamous cell
carcinoma
Larynx
 Squamous intraepithelial lesions
◦ May complain hoarseness
◦ Examination shows thickening of the surface
 Mild dysplasia – slight nuclear abnormality
 Moderate dysplasia – more marked than mild
abnormality
 Severe – marked nuclear abnormality
 Carcinoma in situ – full thickness involvement
Squamous intraepithelial lesions
Laryngeal SIL
Larynx
 Invasive carcinoma
◦ 2.2% of all cancers in men; 5th decade and
beyond; 96% males
◦ Smoking is the main risk factor, enhanced by
alcohol consumption
◦ Associated with HPV 16 and 18 in 25 % of
cases
◦ Hoarseness is a common early symptom for
glottic tumor
Larynx, invasive cancer
 MRI and CT scan improves diagnostic
accuracy
◦ Glottic – 60-65% of cases ; arise from true
vocal cords; tends to be localized due to
cartilagenous wall and paucity of lymphatics
◦ Less lymph node metastasis
◦ Treatment is irradiation and surgery
Laryngeal cancer
Squamous cell carcinoma
Larynx and invasive cancer
 Supraglottic – 30-35 % of cases
◦ Involves false cord and ventricle and or
laryngeal and lingual surface of the epiglottis
◦ Average lymph node metastasis is 40 %
◦ Treatment is irradiation and surgery
 Transglottic – less than 5 % of cases
◦ Highest lymph node involvement
Larynx, invasive cancer
 Pathologic features
◦ Grossly, these are protruding pink to gray
mass that is often ulcerated.
◦ Vocal cord lesions tend to have keratotic
apperance
◦ 90% are squamous type
◦ Papillary squamous variant have association
with HPV
Larynx, invasive cancers
 Other microscopic types
◦ Verrucous – polypoid pattern, well
differentiated tumors.
◦ DDx is verrucous hyperplasia
◦ Small cell neuroendocrine CA
◦ Basaloid Squamous Cell Ca
◦ Lymphoepithelioma like carcinoma
◦ Adenocarcinoma
◦ Sarcomatoid carcinoma
Verrucous carcinoma
Prognosis of laryngeal SCCA
 Clinical stage – 5 year survival
◦ Glottic 80 % of cases
 I: 90%, II: 85% III: 60% IV:<5%
 Supraglottic 65% if located in the aryepiglottic fold
(worst prognosis)
 I: 85% II: 75% III: 45% IV: <5%
 Transglottic 50%
 Subglottic 40%
 Microscopic grade – independent prognostic
determinator with stage
Pleura
 Lined by mesothelial cells
 Asbestos and the pleura –
◦ Related to the development of pleural plaque
and mesothelioma ( amosite and crocidolite
fibers)
◦ Used in construction so inhalation is the
mode of acquisition
◦ 2/3 of mesothelioma is associated with
asbestos
Mesothelioma
 Benign papillary mesothelioma is common
in the peritoneal cavity but rare in the
pleura
 Differentiation between malignant and
benign mesothelioma is lack of significant
atypia and well circumscribed solitary
nature of the lesion
Malignant mesothelioma
Usually seen in adults, familial clustering
 Presents with chest pain and pleural
effusion
 Starts from the lower half of a
hemithorax and later spread to the rest
of the cavity
Malignant mesothelioma
 Multiple gray or white ill-defined nodules
in a diffusely thickened pleura
 Pleural effusion is almost always present
 Forms papillae and has invasion( most
reliable criteria of malignancy)
 Need to be distinguished from metastatic
carcinoma from the lungs
 Need to use markers like calretinin
(usually expressed by mesothelium)
Mesothelioma
Mesothelioma
Mesothelioma
Spread and metastasis
 Contiguity and implantation – spread to
the entire pleura)
 If the lesion also involved nodular lesions
WITHIN the lungs, then the primary
mass is probably the lung and not the
pleura
 Distant metastasis is usually late
Treatment and prognosis
 No satisfactory treatment at present but
bulk resection with radiation sometimes
resulted in long-term remission.
 Stage – late poor prognosis
 Gender – poorer in males
 Tumor subtype – spindle and sarcomatous
– shorter survival
Metastatic tumors
 75% of pleural tumors are metastatic
 Dyspnea, cough, chest pain, pleural
effusion in patients over 50 years
 Serosanguinous or hemorrhagic fluid
 Lungs 33%, breast 20%, stomach 7.3 %
 90% of lung, breast and ovarian malignant
effusions are ipsilateral to the primary
lesion
Metastatic tumor, lung
Tumors of the Lung
 90% more than 40 years old
 1.5 – 1 male female ratio
 Cigarette smoking(80%), asbestos,
pulmonary fibrosis, poylcyclic aromatic
hydrocarbons, radiation, air pollution
 Duration and intensity of smoking are
well correlated with cancer risk
 Second hand smoke is also a factor
 Tumors of the lung
 Progression of squamous carcinoma is
squamous basal cell hyperplasia, to
squamous metaplasia, to squamous
dysplasia, to in-situ-carcinoma, and lastly,
invasive carcinoma
 Most lung cancers are of considerable
size when detected
 Signs and symptoms develop late
 In general, calcified “coin lesion” is not
probably carcinoma
Pulmonary mass, imaging
Major categories of lung carcinoma
 1. Squamous cell carcinoma -20%
 2. Small cell carcinoma -14%
 3. Adenocarcinoma including
bronchioloalveolar carcinoma- 38%
 4. Large cell carcinoma- 3%
 5. Adenosquamous carcinoma} and
 6. Sarcomatoid carcinoma} about 25%
Squamous cell carcinoma
 44% males; 25% females
 Most are centered in segmental bronchi
so it present as hilar or perihilar mass in
chest x-ray
 Pneumonitis or atelectasis in more than
half of patients
 Exfoliated malignant cells identified by
sputum or brush cytology
 Calcification extremely unusual
Squamous cell carcinoma
 Highest frequency of TP 53 mutation
 Loss of RB tumor suppressor in 15 % of cases
 CDKN2A is inactivated and p16 is lost in 65 % of
cases
 Growth may be exophytic to produce
intraluminal mass to cause obstruction and
atelectasis or
 Penetrative that invade the wall and along
peribronchial tissue
 Gray white bulky with areas of hemorrhage and
necrosis
Squamous cell carcinoma
 Keratinization and intracellular bridges with
pearls if well differentiated
 Generally arise from the segmental or
subsegmental bronchi
 May also be seen peripherally but not as
common as in adenocarcinoma
 Surgery may help in Adenocarcinoma and
SCCA but not in Small cell Carcinoma and
Large cell Carcinoma
 So treatment in the latter 2 are
chemotherapy and radiation only
Squamous cell carcinoma, lung
Squamous cell carcinoma
Adenocarcinoma
 Higher percentage in females
 Poorly circumscribed gray-yellow lesions,
maybe single or multiple
 May secrete abundant mucin secretion,
cavitation extremely rare
 65% peripherally located, 77% involve
visceral pleura
 Associated with visceral scar
 Lung tumor of non-smokers and usually are
EGFR mutation positive and never have
KRAS mutations
Adenocarcinoma
 Precursor lesions
◦ A. Atypical adenomatous hyperplasia- small
lesion about 0.5 cm
 Dysplastic pneumocytes
 May be single or multiple
◦ B. Adenocarcinoma in situ – formerly called
bronchioloalveolar carcinoma
 Less than 3 cm
 Cells with more dysplasia growing along preexisting
alveolar septae
Adenocarcinoma
 Acinar, lepidic, papillary, micropapillary and
solid with mucin formation
 More peripheral and smaller size compared
to SCCA
 Majority express Thyroid Transcription
Factor-1 (TTF-1)- required for normal lung
development
 Tumor cells crawl along normal alveolar
septae
 Maybe mutiple, solitary or consolidated to
resemble pneumonia
Adenocarcinoma, lung
Adenocarcinoma, lung
Adenocarcinoma (bronchiloalveolar)
lung
Adenocarcinoma, lung
Small cell carcinoma
 Highly malignant
 Strong association to cigarette smoking
(85%)
 No known preinvasive stage
 Typically a lesion of the central portion
but may also be peripherally
 Cells differentiate to neuroendocrine cells
and has wide endocrine related
syndromes
Small cell carcinoma
 Syndromes related
◦ Cushing, inappropriate ADH secretion,
Lambert-Eaton or myasthenia like syndrome
and carcinoid syndrome
 Small cells , ill-defined borders size is
about 25 micra
 IHC: synaptophysin, chromogranin, and
CD57
 Most commonly associated with ectopic
hormone production
Small cell carcinoma, lung
Small cell carcinoma, lung
Large cell carcinoma
 Undifferentiated malignant epithelial
tumor that lacks the cytologic features of
other forms of lung cancer
 Large nuclei,prominent nucleoli and
moderate amount of cytoplasm
 Lack markers associated with either
adenocarcinoma or squamous cell
carcinoma
Secondary pathology
 Focal emphysema due to partial
obstruction
 Atelectasis due to total obstruction
 Bronchitis, bronchiectasis – due to
impaired drainage
 Superior vena caval syndrome –
compression or invasion of the superior
vena cava
Manifestation
 Cough 75%
 Weight loss 40%
 Chest pain 40%
 Dyspnea 20%
 Signs of metastasis are back pain,
headache, hemiparesis, cranial nerve
damage and seizures
Prognosis
 Age – 40 years and younger, very poor
prognosis\
 Sex – women worse due to advanced
lesion
 Location – superior pulmonary sulcus
better; SCCA at the periphery- better
 Tumor size – smaller better
Prognosis
 Squamous cell carcinoma – most curable
 Bronchioloalveolar (adenocarcinoma in
situ – better than ordinary
adenocarcinoma
 Small cell ca – dismal outcome- 5year
survival less than 2%
 Blood vessel invasion – ominous
 Pleural effusion – poor prognosis
Prognosis
 Inflammatory reaction-
lymphoplasmacytic – better
 TTF-1 – strong expression predicts better
survival than NSCLC
 CD117 – in SCCA and adenocarcinoma –
high degree of proliferation and denotes
aggressiveness
Pleural effusion
Pleural effusion
Malignant cells in pleural fluid