Lung Path 5 - Pulm Tumors and Pleural Diseases (Singh) Flashcards
(112 cards)
1
Q
What is more common primary pleural tumors or secondary tumors from metastasis?
A
Secondary from metastasis
2
Q
The most frequent metastatic malignancies of the pleura arise from which 2 sites?
A
Breast and lung
3
Q
In most metastatic involvements of the pleura what type of effusion follows?
A
Serous or sero-sangioneous often containing neoplastic cells
4
Q
Which soft-tissue tumor has a propensity to occur in the pleura is often attached to the surface by a pedicle?
A
Solitary fibrous tumor
5
Q
Which immunostaining features of solitary fibrous tumors are helpful in distinguishing these tumors from malignant mesotheliomas?
A
CD34+ and keratin-negative
6
Q
What do solitary fibrous tumors show microscopically?
A
Whorls of reticulin and collagen fibers w/ interspersed spindle cells resembling fibroblasts
7
Q
Solitary fibrous tumors are highly associated with a cryptic inverion of which chromosome and this creates which fusion gene unique to this tumor?
A
Chromosome 12 —> NAB2-STAT6 fusion gene
8
Q
Homozygous deletion of which tumor suppressor gene occurs in about 80% of mesothelioma; involves which chromosome?
A
CDKN2A/INK4-α on chromosome 9p
9
Q
How does malignant mesothelioma appear grossly?
A
Affected lung is ensheathed by a thick layer of soft, gelatinous, grayish-pink tumor tissue
10
Q
What are the 3 variants of growth that can be seen microscopically with mesothelioma?
A
- Epithelioid
- Sarcomatoid
- Mixed
11
Q
Epithelioid type of mesothelioma resembles adenocarcinoma; how can it be differentiated via immunohistochemical stains for which 5 markers?
A
- (+) Keratin
- (+) Calretinin
- (+) Wilms tumor 1 (WT-1)
- (+) Cytokeratin 5/6
- (+) D2-40
12
Q
The mesenchymal type of mesothelioma (sarcomatoid type) appears as what type of sarcoma and resembles?
A
Spindle cell sarcoma, resembling fibrosarcoma
13
Q
Sarcomatoid mesotheliomas may only stain positive for which marker?
A
Keratin
14
Q
What are the typical presenting features of malignant mesothelioma?
A
- Chest pain
- Dyspnea
- Recurrent pleural effusions**
15
Q
Malignant mesothelioma often invades lung directly and commonly metastasizes to which LN and organs?
A
- Hilar LN’s
- Eventually –> liver and other distant organs
16
Q
What is the prognosis of malignant mesothelioma?
A
50% die within 12 months; few survive longer than 2 years
17
Q
What are found in increased numbers in the lungs of patients with mesothelioma?
A
Asbestos bodies and asbestos plaques
18
Q
What is the major morphological pattern of damage seen with chronic rejection following a lung transplant?
A
Bronchiolitis obliterans –> fibrosis causing partial or complete occlusion of small airways WITH or WITHOUT active inflammation
20
Q
What age is the peak incidence of lung cancer seen?
A
50-60 y/o
21
Q
Deletions of which 3 chromosomal loci and 3 genes are seen as early events in the squamous cell carcinoma of the lung
A
- 3p and 9p (site of CDKN2A gene –> product = p16)
- -* 17p (site of TP53 gene)
- -* Loss of RB tumor suppressor
22
Q
Large areas of “benign” respiratory mucosa being mutagenized by exposure to carcinogens in tobacco smoke is known as what?
A
“Field effect“
24
Q
Loss of function mutations in which 2 genes and chromosome are seen with small cell carcinoma of the lung?
A
- TP53
- RB
- Chromosome 3p deletions
25
Q
Amplification of which gene has been associated with squamous cell carcinoma of the lung?
A
FGFR1
26
Q
Oncogenic gain of function mutations in which 5 RTK genes are associated with Adenocarcinoma of the lung?
Tumors without RTK mutations often have mutation in which gene?
A
- RTK mutation = EGFR + ALK + ROS + MET and RET
- Non-RTK = KRAS
27
Which type of lung cancer shows the **strongest** association with smoking?
**Small cell carcinoma**
29
Amplification of which gene is associated with small cell carcinoma of the lung?
***MYC*** family
30
Which precursor lesion is characterized by **dysplastic pneumocytes** lining alveolar walls that are **mildly fibrotic**?
**Atypical adenomatous hyperplasia**
31
Which precursor lesion is composed **entirely** of **dysplatic** cells growing **confluently** along pre-existing alveolar septae; and may or may not hav intracellular mucin?
**Adenocarcinoma in situ**
33
Which tumor of the lung tends to spread **aerogenously**, forming satellite tumors and **may consolidate an entire lobe mimicking lobar pneumonia**?
**Mucinous ADENOCARCINOMA**
34
What is the characteristic histologly of squamous cell carcinoma?
**Keratin pearls** and/or **intracellular bridges**
35
Via cytology which color will the cytoplasm be if keratin is present and is indicative of SCC?
**Orange** cytoplasm
36
Lung cancers in **never** smokers are more common in which sex and are most often what type of cancer?
- **Women**
- **Adenocarcinoma**
37
Lung cancers in **never** smokers are **more likely** to have mutations in which gene and **never** have mutations in what?
- **More** likely to have ***EGFR*** mutations; sometimes ***TP53***
- **NEVER** have ***KRAS*** mutations
38
What is the histology of the chromatin, cytoplasm, nucleus, and nucleoli like with small cell carcinoma of the lung?
- Small cells w/ **scant cytoplasm**
- Finely **granular (BLUE) nuclear chromatin** (**salt and pepper** pattern)
- **Absent** nucleoli
- **Necrosis is COMMON** and often **extensive**
39
Which type of lung cancer is more commonly arising in the **peripheral** lung and which in the **central**/**hilar** lung?
- **Peripheral** = adenocarcinoma
- **Central/hilar** = squamous cell carcinoma
40
**Basophilic** staining of vascular walls due to encrustation by DNA from necrotic tumor cells (**Azzopardi effect**) is common with what lung tumor?
**Small cell carcinoma**
43
Majority of adenocarcinomas of the lung express which transcription factor required for normal lung development?
**Thyroid transcription factor-1**
47
Which type of lung tumor is almost always metastatic at time of presentation and is best treated with specific chemotherapies/radiation?
Small cell \*neuroendocrine\* carcinoma
48
What is the most aggressive lung tumor with **no** known preinvasive phase?
Small cell \*neuroendocrine\* carcinoma
50
What is a more **ominous** change squamous metaplasia or dysplasia?
**Dysplasia**
52
Which 3 markers are found in the neurosecretory granules of small cell carcinomas of the lungs?
- Chromogranin
- Synaptophysin
- CD57
53
Via immunohistochemistry high levels of which anti-apoptotic protein can be demonstrated in small cell carcinomas of the lung?
**BCL2**
54
Early distant spread of lung carcinoma generally occurs via which 2 pathways; which carcinoma specifically metastasizes late?
- **Lymphatic** and **hematogenous**
- **Squamous cell carcinoma** spreads **late**
55
What characteristic of Lambert-Eaton Syndrome distinguishes it from Myasthenia Gravis?
**Sx's IMPROVE** w/ **more** movement throughout the day
56
Apical lung cancers (**pancoast tumors**) in the superior pulmonary sulcus tend to invade which neural structures around the trachea and produce what signs/sx's?
- Invade **cervical sympathetic plexus**
- **Severe pain** in the distribution of the **ulnar nerve**
- **Horner syndrome** --\> **enophthalmos + ptosis + miosis + anhidrosis**
57
What are the 4 favored sites of metastasis for lung carcinomas?
- **Adrenals**
- **Liver**
- **Brain**
- **Bone**
58
Which 3 LN's are common sites of metastasis for lung carcinoma?
- **Bronchial**
- **Tracheal**
- **Mediastinal**
59
What may **partial** or **total** obstruction caused by a lung carcinoma cause?
- **Partial** --\> **focal emphysema**
- **Total** --\> **atelectasis**
60
Impaired drainage of the airways caused by lung carcinomas is a common cause of what?
**SEVERE suppurative** or **ulcerative bronchitis** or **bronchiectasis**
61
What is the main difference between Diffuse Idiopathic Pulmonary Neuroendocrine Cell Hyperplasia (DIPNECH) and Carcinoid tumors?
- **SIZE!!!**
- **DIPNECH** = **very** small, **\<5mm** ---\> **"Tumorlets**"
- **Carcinoid tumor** = **5mm** or **larger**
62
Venous congestion of the head and arm w/ circulatory compromise caused by an underlying lung carcinoma is known as what?
**SVC syndrome**
63
Which tumor of the lungs grows as **fingerlike** or **spherical** **polypoid masses** that commonly project into the lumen of the bronchus and may produce so-called **collar-button lesions**?
Carcinoid tumor
64
Which lung tumor is characterized by organoid, trabecular, palisading, ribbon, or rosette-like arrangements of cells w/ uniform round nuclei and abundant cytoplasm separated by a delicate fibrovascular stroma?
Carcinoid tumor
65
What are features of atypical carcinoid tumors (neuroendocrine tumor grade 2) which differ from typical carcinoid tumors (grade 1)?
- ↑↑↑ **mitotic activity**
- **NECROSIS** (typical carcinoids **lack** necrosis)
- **Disordered growth**
- ↑↑↑ rate of **metastasis** w/ **LOWER survival**
66
Phrenic nerve invasion by lung tumor is associated with what?
**Diaphragm paralysis**
67
Activating mutations of which gene in lung cancers is associated with a **worse prognosis** regardless of tx?
***KRAS***
68
Release of PTHrP leading to paraneoplastic **hypercalcemia** is associated with what type of lung tumor?
Squamous cell carcinoma
69
Which 2 hormones may be secreted by small cell carcinomas and what does each cause
- **ADH** ---\> **SIADH**
- **ACTH** ---\> **Cushing Syndrome**
70
What is a feature that can be seen on CXR and CT that points to metastasis **TO** the lung?
**Multiple** discrete nodules (**cannonball lesions**) scattered throughout all lobes
71
How are lung hamartomas most often discovered and how do they appear?
- **Incidental** finding on CXR
- Appear as **rounded, radio-opacity ("coin lesion")**
72
What do pulmonary hamartomas consist of?
**Nodules** of CT; most often **cartilage**, also **fat** and **fibrous tissue;** intersected by **epithelial clefts**
73
Which 2 chromosomal aberrations are associated with lung hamartomas?
- **6p21**
- **12q14**-**q15**
74
What are 2 systemic nervous system related syndromes that may be associated with lung tumors?
- **Lambert-Eaton myasthenic syndrome** --\> auto-abs against Ca2+ channels --\> **muscle weakness**
- **Peripheral neuropathy** --\> usually **purely** sensory
75
What is a dermatologic manfiestation that may be associated with lung tumors?
**Acanthosis nigricans**
76
Lymphangioleiomyomatosis is characterized by proliferation of which cells and what does this create morphologically?
**Perivascular epithelioid cells** --\> **CYSTIC**, emphysema-like **dilation** of terminal air spaces, thickening of interstitium, and obstruction of lymph vessles
77
Lymphangioleiomyomatosis is associated with loss of function of which tumor suppressor; this tumor suppressor is normally a negative regulator of what?
***TSC2*** --\> neg. regulator of **mTOR activity**
79
Diffuse involvement of both lungs with cystic, emphysem-like dilation of airspaces in Lymphangioleiomyomatosis, may present with what complication?
Pneumothorax
81
What are 2 hematologic abnormalities that may be assocaited with lung tumors?
- **Leukemoid rxns**
- **Trousseau syndrome** (DVT and thromboembolism)
82
What is a peculiar abnormality of connective tissue associated with lung tumors and what is seen with this?
**Hypertrophic pulmonary osteoarthropathy** --\> **clubbing** of fingers
83
Lambert-Eaton Syndrome is most often associated with what tumor of the lung?
**Small cell carcinoma**
84
Trousseau sign (migratory thrombophlebitis) is most often associated with what type of lung tumor?
Adenocarcinoma
86
Why is it important to differentiate DIPNECH from Carcinoid tumors?
**Carcinoid tumors** have ability to **metastasize**
90
Immunohistochemical stains of carcinoid tumors may be positive for what 4 markers?
- **Serotonin**
- **Neuron-specific enolase**
- **Calcitonin**
- **Bombesin**
91
What are clinical features of carcinoid tumors which may result from their intraluminal growth?
- **Persistent** cough
- **Hemoptysis**
- Impairment of drainage of resp. pathways --\> 2' infections
- **Bronchiectasis**
- **Emphysema**
- **Atelectasis**
92
What are the sx's of Carcinoid Syndrome?
- Flushing
- Diarrhea
- Cyanosis
93
What is the prognosis like for typical carcinoid vs. atypical carinoid tumors?
- **Typical** have 5-year survival of **95%**
- **Atypical** have 5-year survival of **70%**
98
Lymphangioleiomyomatosis is a lung disorder occurring almost exclusively in whom?
**Young women**
99
Which markers are expressed by Lymphangioleiomyomatosis?
**Melanoma**, like **HMB-45** and **smooth muscle cells**
102
What is the only definitive tx currently available for Lymphangioleiomyomatosis?
Lung transplant
104
The strong tendency for Lymphangioleiomyomatosis to affect young women suggests what hormone contributes to proliferation of perivascular epithelioid cells?
Estrogen
105
Inflammatory myofibroblastic tumors, though rare, is more common in whom; presents how?
- **Children**
- **Fever + cough + chest pain** + **hemoptysis**
- May be **asymptomatic**
106
Imaging of a child with suspected Inflammatory myofibroblastic tumor will show what?
**Single** (rarely multiple) **round**, well-defined, **peripheral mass** that often has **calcium** deposits
107
Inflammatory myofibroblastic tumors are associated with activating rearrangements of which gene and on which chromosome?
***ALK*** gene on **chromosome 2p23**
108
Growth of contiguous tumors (aka direct continuity) into the lungs most often occurs with what 2 types of tumors?
- Esophageal carcinomas
- Mediastinal lymphomas
109
Radiation used in therapy for tumors in the lung or mediastinum often causes what type of pleuritis?
**Serofibrinous** pleuritis
110
A purulent pleural exudate (**empyema**) usually results from what?
**Bacterial** or **mycotic** seeding of the pleural space; by **contiguous** spread from **intrapulmonary** infections, but may also be from **lymphatic** or **hematogenous** dissemination
111
Which inflammatory-type of pleural effusion is characterized by **loculated, yellow-green, creamy pus** composed of masses of neutrophils admixed with other leukocytes?
**Empyema**
112
Empyema of the lungs may resolve, but more often the exudate organizes into what; causes what complications?
- Organizes --\> **dense, tough fibrous adhesions**
- Frequently **obliterate** the **pleural space** or **envelope** the lungs
- **Restricting pulmonary expansion**
115
What are the 3 major mechanisms underlying transudative pleural effusions; examples?
- ↑ hydrostatic pressure; "overflow" from the lung interstitium = **CHF**
- ↓ plasma oncotic pressure = **nephrotic syndrome**
- Movement of transudative ascitic fluid thru the diaphargam = **cirrhosis**
116
What are the 2 major mechanisms underlying exudative pleural effusions; some examples?
- **Inflammation** --\> infection (TB, pneumonia), PE (infarction), CT disease (SLE, RA), adjacent to subdiaphragmatic disease (pancreatitis, subphrenic abscess)
- **Malignancy**
117
What is the arrow indicating on this CT scan?
Pleural effusion
118
How will a pleural effusion associated with mediastinal carcinomatosis appear grossly due to **decreased** lymph drainage?
**Milky chylous** effusion = **Chylothorax**
119
Noninflammatory collections of serous fluid within pleural cavities are known as what; appear how grossly?
**Hydrothorax**; clear fluid that is straw colored
120
What is the most common cause of hydrothorax; other causes?
- **Most common** = Cardiac failure
- Also, **renal failure** and **cirrhosis**
121
Which type of pleuritis is manifested by sanguineous inflammatory exudates?
Hemorrhagic pleuritis
122
Hemorrhagic pleuritis is found in what 3 settings?
- Hemorrhagic diatheses
- **Rickettsial** diseases
- **Neoplastic** involvement
123
Spontaneous idiopathic penumothorax most often occurs in which age group and is due to what?
- **Young patients**
- **Rupture** of small, peripheral, usually **apical subpleural blebs**
125
When injury to chest wall results in a one-way valve allowing air into the pleural space, but not out, effectively acting as a pump and ↑ pressure, this is known as?
**Tension pneumothorax**
126
A tension pneumothorax is due to expansion of which structure?
Chest wall (not lungs per se)
127
What is one of the more devastating consequences of Empyema that makes it hard to treat and hard to clear out?
Creating **loculations** --\> **web-like** traps for fluid
128
What type of pneumothorax is this?
**Primary pneumothorax**
129
What type of pneumothorax is this?
**Tension** pneumothorax
130
Which type of pneumothorax is associated with pleural cavity pressure is \< atmospheric pressure?
Pleural cavity pressure \> atmospheric pressure?
- Pleural cavity \< atmospheric = **primary** pneumothorax
- Pleural cavity \> atmospheric = **tension** pneumothorax
131
In spontaneous idiopathic pneumothorax which direction will the trachea shift?
**TOWARD** the side of collapse
135
Which soft-tissue tumor has a propensity to occur in the pleura is often attached to the surface by a pedicle?
Solitary fibrous tumor
137
What do solitary fibrous tumors show microscopically?
**Whorls** of **reticulin** and **collagen** fibers w/ interspersed **spindle cells** resembling **fibroblasts**
139
Hemothorax is a usually fatal complication associated with what?
**Ruptured** **aortic aneurysm** or **vascular trauma**
140
How does malignant mesothelioma appear grossly?
Affected lung is **ensheathed** by a **thick layer** of **soft, gelatinous**, **grayish-pink** tumor tissue
141
What are the 3 variants of growth that can be seen microscopically with mesothelioma?
- Epithelioid
- Sarcomatoid
- Mixed
142
Epithelioid type of mesothelioma resembles adenocarcinoma; how can it be differentiated via immunohistochemical stains for which 5 markers?
- (+) **Keratin**
- (+) **Calretinin**
- (+) **Wilms tumor 1 (WT-1)**
- (+) **Cytokeratin 5/6**
- (+) **D2-40**
143
Pneumothorax is most commonly associated with what 3 conditions?
- Emphysema
- Asthma
- Tuberculosis
145
Typical course of spontaneous idiopathic penumothorax; and likelihood or recurrence?
- Typically **subsides spontaneously** as air is resorbed
- **Reccurent attacks** = **common**
