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[Type here] Patho 2 TUMORS OF THE HEAD AND NECK

Clinical AND ADVANCE pathology


TOPIC: TUMORS OF THE LUNGS 6.03

TUMOURS OF THE LUNGS


• Notes: A variety of benign and malignant tumors may arise in the lung, but 90% to
95% are carcinomas, about 5% are bronchialcarcinoids, and 2% to 5% are mesenchymal and othermiscellaneous neoplasms.
• Most frequently diagnosed major cancer in the world
• Most common cause of cancer mortality worldwide

ETIOLOGY:
• Most associated with cigarette smoke
• 80% of lung cancers occur in active smokers or those who stopped recently
• Nearly linear correlation bet frequency and # of pack years
• Develops in 11% of heavy smokers
• Women – higher suspectibility
• Quitting decreases risk, but never to baseline levels
• Second-hand smoke: twice the risk of CA as nonsmokers
• Cigar and pipe smoking also carry risk, but less than cigarette
• Smokeless tobacco – spare the lung but cause oral cancers and nicotine addiction
• Industrial hazards
• Asbsestos, arsenic, chromium, uranium, nickel, vinyl chloride, mustard gas
• Lung CA is mc malignancy in people exposed to asbsestos (5x), esp when they also smoke (55x)

In never smokers:
– 25% of lung CA
– More commonly women, most are adenocarcinomas
– More likely to have EGFR mutations, almost never KRAS mutations

• Histologic classification
– Adenocarcinoma (38%)
– Squamous cell carcinoma (20%)
– Small cell carcinoma (14%)
– Large cell carcinoma (3%)
– Other (25%)

Transcribed by: John Velasco, Fabee Tesnado, Bryan Rayo, Aivee Reyes, Gab Dalumpines #pusongpalaban2019, #makingEAC-SMgreatAgain!
If you want a copy, there is no problem to ask the transcriber a copy of this. 
So do not fear, for I am with you; do not be dismayed, for I am your God. I will strengthen you and help you; I will uphold you with my righteous right hand.- Isaiah 41:10
[Type here] Patho 2 TUMORS OF THE HEAD AND NECK

TUMOR EPIDEMIOLOGY ETIOLOGY/ PATHOGENESIS MORPHOLOGY


CLINICAL MANIFESTATION
ADENOCARCINOMA - Most common type 1. Atypical adenomatous hyperplasia KRAS mutations occur
of lung CA in 2. Adenocarcinoma in situ (formerly primarily in
women and non- bronchioloalveolar carcinoma) adenocarcinoma
smokers (Robbins).
- • Acinar, lepidic, papillary,
- Malignant epithelial micropapillary, solid w/ mucin
tumor with glandular formation hypothesis:
differentiation or mucin • Majority express thyroid Adenocarcinoma of the
production transcription factor-1 (TTF-1) lung arises from
atypical adenomatous
o Lesions are more peripherally located hyperplasia
and smaller progressing to
Lepidic: grows like butterflies resting on a picket-fence/stem, only seen in
slowly than SCCA but tend to metastasize bronchioloalveolar
adenocarcinoma in situ
widely and earlier carcinoma which then
Various patterns: acinar, lepidic, papillary, micropapillary, and solid tumor with
transforms into invasive
mucin formation
that are less than 0.5 mm, curable adenocarcinoma
(Robbins).
small
glands floating on a pool of mucin
Majority are positive for TTF-1, 80%
contain mucin

o Thyroid Transcription Factor: protein


produced by lungs, useful because it can
establish whether the primary tumor came
from the lungs, or from other organs
.
SQUAMOUS CELL • Most commonly – Precursors: Ch deletions in tumor
CARCINOMA in men Squamous metaplasia, dysplasia, suppressor loci
• Strongly carcinoma in situ (CDKN2A, TP53, FGFR-
associated with 1)
smoking Notorious for producing paraneoplastic
Highest frequency of p53
• Most common syndrome of hypercalcemia and pancoast
mutations (Robbins).
location: tumor o Pancoast tumor: located at superior
centrolobular sulcus of the upper lung
compared to other cancers • Arise centrally, Histologically, presence of keratinization and/or
intercellular bridges
Transcribed by: John Velasco, Fabee Tesnado, Bryan Rayo, Aivee Reyes, Gab Dalumpines #pusongpalaban2019, #makingEAC-SMgreatAgain!
If you want a copy, there is no problem to ask the transcriber a copy of this. 
So do not fear, for I am with you; do not be dismayed, for I am your God. I will strengthen you and help you; I will uphold you with my righteous right hand.- Isaiah 41:10
[Type here] Patho 2 TUMORS OF THE HEAD AND NECK
– Squamous pearls
– Or individual cells with dense pink cytoplasm

SMALL CELL Strong association with • Highly malignant – most aggressive P53 and RB1 tumor
CARCINOMA smoking compared to • Strong relationship to smoking suppressor genes are
SCCA o Only about 1% of – Only 1% occurs in nonsmokers frequently mutated.
those with small cell CA are Immunohistochemistry
– Major bronchi or periphery
nonsmokers demonstrates high levels of
• Most commonly associated with anti-apoptotic protein
No precursor lesion, ectopic hormone production BCL2 (Robbins). •
very hard to detect tumor • Histologically, small cells with scant cytplasm, ill-defined cell borders,
early on “salt and pepper” nuclear chromatin, absent or inconspicuous nucleoli
• High mitotic count
• Neither glandular nor squamous differentiation
paraneoplastic syndrome o • Necrosis common and extensive
ACTH & ADH • Azzopardi effect – basophilic staining of vascular walls due to encrustation
by DNA from necrotic tumour cells
radiation
and chemotherapy
LARGE CELL • Undifferentiated malignant epithelial
CARCINOMA tumour that lacks cytologic features
of the other forms of cancer
• Diagnosis of exclusion
• TTF-1, Napsin A - negative
• p63, p40 - negative
The cells typically have large nuclei, prominent nucleoli, and a moderate amount of
• Large nuclei, prominent nucleoli, cytoplasm (Robbins).
moderate cytoplasm
• Variant: Large cell neuroendocrine o Organoid nesting, trabecular, rosette-like, and palisading patterns
carcinoma - molecular features o Suggest neuroendocrine differentiation
similar to small cell carcinoma, but
larger cells

LUNG CANCER • Secondary pathologic changes:


– Focal emphysema (if partial
obstruction), atelectasis (if
complete)
– Suppurative/ulcerative
bronchitis/bronchiectasis
– Pulmonary abscesses
– Superior vena cava
syndrome
– Pericarditis, pleuritis
Transcribed by: John Velasco, Fabee Tesnado, Bryan Rayo, Aivee Reyes, Gab Dalumpines #pusongpalaban2019, #makingEAC-SMgreatAgain!
If you want a copy, there is no problem to ask the transcriber a copy of this. 
So do not fear, for I am with you; do not be dismayed, for I am your God. I will strengthen you and help you; I will uphold you with my righteous right hand.- Isaiah 41:10
[Type here] Patho 2 TUMORS OF THE HEAD AND NECK
• Major signs and symptoms:
– Cough (75%)
– Weight loss (40%)
– Chest pain (40%)
– Dyspnea (20%)
– Other symptoms related to
metastasis
• Prognosis is poor
– 5-year survival 52% if
localized, 22% if regional
metastasis, 4% if with distal
metastasis
– In general, adenocarcinoma
and squamous cell
carcinoma tend to remain
localized longer
– Small cell carcinoma – die
within 6 to 17 weeks
• Sensitive to radiatx
and chemo (cure
rates of 15-25% for
limited disease)
– Adenocarcinoma – targeted
therapy in EGFR mutations
(15% of patients) and other
mutated kinases
– KRAS mutations (30%)
worse prognosis regardless
of treaatment
• Paraneoplastic syndromes – in 1 to
10%
– ADH – hyponatremia
– ACTH – Cushing syndrome
– ParaTH, Parathyroid
hormone related peptide
(PRP), prostaglandin E –
hypercalcemia
– Calcitonin - hypocalcemia
– Gonadotropins –
gynecomastia

Transcribed by: John Velasco, Fabee Tesnado, Bryan Rayo, Aivee Reyes, Gab Dalumpines #pusongpalaban2019, #makingEAC-SMgreatAgain!
If you want a copy, there is no problem to ask the transcriber a copy of this. 
So do not fear, for I am with you; do not be dismayed, for I am your God. I will strengthen you and help you; I will uphold you with my righteous right hand.- Isaiah 41:10
[Type here] Patho 2 TUMORS OF THE HEAD AND NECK
– Serotonin and bradykinin –
carcinoid syndrome
• Paraneoplastic syndromes
– ACTH and ADH – usually
small cell carcinomas
– Hypercalcemia – usually
squamous cell carcinomas
• OTHER SYSTEMIC
MANIFESTATIONS
• Lambert Eaton syndrome – muscle
weakness due to autoantibodie, prob
elicited by tumor ionic channels
• Peripheral neuropathy
• Acanthosis nigricans
• OTHER SYSTEMIC
MANIFESTATIONS
• Leukemoid reactions
• Hypercoagulable states
– Trousseau syndrome – DVT
and thromboembolism
• Hypertrophic pulmonary
osteoartropathy – clubbing of fingers
• Pancoast tumour – apical lung cancer
invading the neural structures around
the trachea, producing findings like
severe ulnar nerve pain and Horner
syndrome (enophthalmos, ptosis,
miosis, anhidrosis)

Carcinoid tumor Low grade, malignant Typical vs. atypical, carcinoid syndrome o
neuroendocrine tumor They only differ in number of mitosis seen and
appearance of cell

pop Typical- less mitotic figures and cells are


arranged in an Organoid fashion Shows tumor cells that are relatively bland looking, very uniform in size, pleomorphism and
- mitosis is not that easily seen, and arranged in an organoid fashion, separated thinly by
smoker Atypical- more mitotic figures and cells are fibrovascular septa.
more disorganized. Loses its low grade
potential, can become malignant and has
capacity to metastasize.
Hamartoma Most important
miscellaneous lung tumor
Transcribed by: John Velasco, Fabee Tesnado, Bryan Rayo, Aivee Reyes, Gab Dalumpines #pusongpalaban2019, #makingEAC-SMgreatAgain!
If you want a copy, there is no problem to ask the transcriber a copy of this. 
So do not fear, for I am with you; do not be dismayed, for I am your God. I will strengthen you and help you; I will uphold you with my righteous right hand.- Isaiah 41:10
[Type here] Patho 2 TUMORS OF THE HEAD AND NECK
It is usually a peripheral lung mass composed
agnosed as an of normal pulmonary tissue components such as
incidental anatomical smooth muscle and collagen. They are more
common in men than in women and have a peak
neoplasm because cells are incidence in the 60s. They are often incidental
monoclonal radiographic findings as solitary nodules. They
have a pathognomonic “popcorn” pattern of
calcification in some cases; however, without
lesion: o Solitary, <3-4cm, such a finding, resection is necessary to rule out
malignancy, especially in smokers.
Composed of cartilage,
glands, and any cells which
are typically seen on lungs
Lymphagioleiomyomatosis Very rare Is a perivascular epithelioid cells leading to
young women cystic, emphysemalike dilation of terminal
airspaces, thickening of the interstitium, and
obstruction of lymphatic vessels
Pulmonary LAM is a rare
condition that afflicts It is often misdiagnosed as asthma or chronic
premenopausal women and obstructive pulmonary disease. Pathologically,
should be suspected in LAM is characterized by the proliferation of
young women with atypical pulmonary interstitial smooth muscle
“emphysema,” recurrent and cyst formation. The immature-appearing
pneumothorax, or chylous smooth-muscle cells react with monoclonal
pleural effusion. antibody HMB45, which recognizes a 100-kDa
glycoprotein(gp100) originally found in human
melanoma cells.
Pleural Tumors Most important Pleural asbestosis Has 3 Histologic Types:
Solitary fibrous tumor- tumor. Common sign and symptoms: Chest pain, o Epitheloid type- It may ay form gland which makes it hard to distinguish from
Malignant Mesothelioma dyspnea, and, recurrent pleural effusions adenocarcinoma need to do immunohistochemistry stain.
50% die within 12 months o Sarcomatoid Type – spindle-elongated cells
of diagnosis o few survive Aggressive therapy seems to improve o Biphasic type – combination of epitheloid and sarcomatoid
longer than 2 years prognosis in some patients. o It may also arise
in peritoneum, pericardium, tunica vaginalis,
and genital tract

Transcribed by: John Velasco, Fabee Tesnado, Bryan Rayo, Aivee Reyes, Gab Dalumpines #pusongpalaban2019, #makingEAC-SMgreatAgain!
If you want a copy, there is no problem to ask the transcriber a copy of this. 
So do not fear, for I am with you; do not be dismayed, for I am your God. I will strengthen you and help you; I will uphold you with my righteous right hand.- Isaiah 41:10
[Type here] Patho 2 TUMORS OF THE HEAD AND NECK
(A)Gross: tumor enclosing the lung parenchyma is pink-white very fleshy tumor. (B)
Epitheloid type. Form glands which make it hard to distinguish from adenocarcinoma. (C)
Sarcomatoid type: spindle-elongated cells.

Transcribed by: John Velasco, Fabee Tesnado, Bryan Rayo, Aivee Reyes, Gab Dalumpines #pusongpalaban2019, #makingEAC-SMgreatAgain!
If you want a copy, there is no problem to ask the transcriber a copy of this. 
So do not fear, for I am with you; do not be dismayed, for I am your God. I will strengthen you and help you; I will uphold you with my righteous right hand.- Isaiah 41:10