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Respiratory Medicine Midterm > The Lung Part 10 > Flashcards

The Lung Part 10 Flashcards

1
Q

Small cell carcinoma

A
  • highly malignant tumor with strong relationship to cigarette smoking!!
  • can arise in major bronchi or in periphery of lung
  • no known pre-invasive phase
  • MOST AGGRESSIVE of lung tumors, metastasizing widely; always fatal!
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2
Q

Small cell carcinoma is comprised of (morphology)

A
  • relatively small cells with scant cytoplasm, ill-defined cell borders, finely granular nuclear chromatin (salt and pepper pattern) and absent or inconspicuous nucleoli
  • cells are round, oval, spindle shaped and nuclear molding is prominent
  • high mitotic count
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3
Q

How do small cell carcinoma cells grow (pattern)? What is common in SCC?

A
  • grow in clusters that exhibit neither glandular nor squamous organization
  • Necrosis is common and often extensive
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4
Q

Azzopardi effect

A

-in SCC, the presence of basophilic staining of vascular walls due to encrustation by DNA from necrotic tumor cells

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5
Q

Grading of small cell carcinomas

A

-All are high grade!

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6
Q

Combined small cell carcinoma

A

-variant in which typical small cell carcinoma is mixed with non small cell histologies like large cell neuroendocrine carcinoma and even spindled cell morphologies resembling sarcoma

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7
Q

EM of small cell carcinoma

A

-dense core neurosecretory granules in 2/3 of cases

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8
Q

small cell carcinoma originates from what kind of cells? How do we know this?

A
  • originates from neuroendocrine progenitor cells which are present in the lining bronchial epithelium
  • know this bc of:
  • -occurrence of neurosecretory granules
  • -expression of neuroendocrine markers like chromogranin, synaptophysin and CD57
  • -ability of tumor to secrete hormones (parathormone-related protein, cause of paraneoplastic hypercalcemia)
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9
Q

Of the lung cancers, which one is most commonly associated with ectopic hormone production?

A

-Small cell carcinoma

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10
Q

Immunohistochemistry demonstrates high levels of ____ protein _____ in 90% of SCC tumors

A

-anti-apoptotic protein BCL2

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11
Q

Large cell carcinoma

A
  • undifferentiated malignant epithelial tumor that lacks cytologic features of other forms of lung cancer
  • large nuclei, prominent nucleoli, moderate cytoplasm
  • Dx of exclusion since doesn’t express any of the markers associated with adenocarcinomas (TTF-1, napsin A) or squamous cell carcinomas
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12
Q

Large neuroendocrine carcinoma

A
  • variant of LCC

- molecular features similar to SCC but cells are larger

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13
Q

Any type of lung carcinoma may extend on to the

A
  • pleural surface and then within the pleural cavity or into the pericardium
  • Metastases to the bronchial, tracheal, and mediastinal nodes can be found in most cases
  • 50% nodal involvement
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14
Q

Distant spread of lung carcinomas occurs through

A
  • both lymphatic and hematogenous pathways
  • often spread early throughout body EXCEPT squamous cell carcinoma which metastasizes outside the thorax LATE
  • No organ spared, but almost always involves ADRENALS
  • Liver, brain and bone are additional favored sites
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15
Q

Combined carcinoma

A

-10% of all lung cancers have combined histology of the other types of carcinomas (adeno, squamous, small cell etc)

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16
Q

Secondary pathology associated with lung cancer

A
  • Local effects distal to bronchial involement
  • Partial obstruction–> FOCAL EMPHYSEMA
  • Total obstruction–>atelectasis
  • impaired airway drainage–>severe suppurative or ulcerative bronchitis or bronchiectasis
  • Pulmonary abscesses
  • SVC Compression/invasion–>venous congestion/edema leading to circulatory compromise (SVC SYNDROME)
  • Extension to pericardial or pleural sacs may cause pericarditis or pleuritis with significant effusions
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17
Q

Clinical course of lung cancer

A
  • slow and aggressive
  • found in patients in their 50s or older whose symptoms are of several months duration
  • CC: cough, weight loss, chest pain, dyspnea
  • Commonly discovered by secondary spread of primary or neoplastic neoplasm elsewhere
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18
Q

Symptoms of metastases in lung cancer

A
  • depends on site
  • back pain in bone metastasis
  • Headache, hemiparesis, CN damage and seizures in brain metastasis
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19
Q

Lung cancer prognosis

A

-Poor prognosis–5 yr survival=16%
-early detection trial produced 20% reduction in lung cancer related mortality by screening high risk pts.
-

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20
Q

prognosis of adenocarcinoma and squamous cell carcinoma vs undifferentiated cancers

A

-Adenocarcinomas and squamous cell carcinomas remain localized longer so have slightly better prognosis than undifferentiated cancers which are usually advanced by the time they are discovered

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21
Q

How to prolong survival in adenocarcinoma of the lung

A
  • Target treatment against activating mutations in EGFR or other tyrosine kinase with specific inhibitors of mutated kinases
  • many tumors that recur carry new mutations resistant to such inhibitors–evidence that the drugs are hitting target
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22
Q

Activating ____ mutations (present in 30% of adenocarcinomas??) associated with a worse prognosis, regardless of treatment

A

KRAS mutations=worse prognosis

23
Q

the survival time with small-cell carcinoma in treated vs. untreated patients?

A
  • 6-17 weeks!
  • very sensitive to radiation therapy and chemotherapy and some have been cured
  • BUT most with SCC have distant metastasis at diagnosis so even with treatment, the mean survival after diagnosis is only 1 year!!
24
Q

Types of hormones elaborated in paraneoplastic syndromes associated with lung carcinoma

A
  • may precede detectable pulmonary lesion
  • ADH: induces hyponatremia
  • ACTH: Cushings
  • Parathormone, parathyroid hormone-related peptide, PGE, and some cytokines: Hypercalcemia
  • Calcitonin: hypocalcemia
  • Gonadotropins: gynecomastia
  • Serotonin and bradykinin: CARCINOID syndrome!
25
Q

Tumors that produce ACTH and ADH are predominantly what kind of carcinomas??

A

-SMALL CELL CARCINOMAS

26
Q

Tumors that produce hypercalcemia are predominantly what kind of carcinomas?

A

-SQUAMOUS CELL CARCINOMAS

27
Q

Lambert-Eaton myasthenic syndrome

A

-muscle weakness caused by auto-Abs (maybe from tumor ionic channels) directed to neuronal calcium channel

28
Q

systemic manifestations of lung carcinoma

A
  • Lambert Eaton myastenic syndrome
  • peripheral neuropathy (purely sensory)
  • dermatologic abnormalities like acanthosis nigricans
  • hematologic abnormalities like LEUKEMOID RXNS
  • hypercoagulable state like TROUSSEAU SYNDROME
  • connective tissue abnormality: HYPERTROPHIC PULMONARY OSTEOARTHROPATHY associated with clubbing of fingers
29
Q

Apical lung cancers in the superior pulmonary sulcus tend to invade

A
  • neural structures around trachea, including cervical sympathetic plexus leading to severe pain in ulnar nerve distribution and HORNER SYNDROME (exophthalmos, ptosis, mitosis, anhidrosis) on same side as lesion
  • these are also called PANCOAST TUMORS
30
Q

Combination chemotherapy is available along with tyrosine kinase inhibitors for those with what genetic mutations?

A

-EGFR, ALK, ROS, and c-MET

31
Q

Tumors 3cm or less w/pure growth along preexisting structures (lepidic pattern) without stromal invasion called

A

-adenocarcinoma in situ

32
Q

Paraneoplastic syndromes are particularly common in what kind of lung cancers

A

SMALL CELL lung cancers

33
Q

The normal lung contains ____ cells within epithelium as single cells or as clusters, the ______

A
  • neuroendocrine cells

- Neuroepithelial bodies

34
Q

Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia

A

-precursor to development of multiple tumor lets and typical or atypical carcinoids

35
Q

Neoplasms of neuroendocrine cells in the lung include

A
  • benign tumorlets–small inconsequential, hyperplastic nests of neuroendocrine cells seen in areas of scarring or chronic inflammation
  • Carcinoids
  • small cell carcinoma
  • Large cell neuroendocrine carcinoma of the lung
36
Q

In contrast to small cell and large cell neuroendocrine carcinomas, carcinoids may occur in patients with

A

-multiple endocrine neoplasia type 1

37
Q

Carcinoid tumors

A
  • younger than 40
  • equal in males and females
  • 20-40% are nonsmokers
  • low grade malignant neoplasms sub classified into typical and atypical carcinoids
38
Q

Carcinoids morphology–Gross

A
  • may arise centrally or peripherally
  • Gross: central tumors grow as fingerlike or spherical polypoid masses that commonly project into lumen of bronchus and are usually covered by intact mucosa
  • rarely exceed 3-4 cm
  • confined to mainstem bronchi but some penetrate bronchial wall to fan out in peribronchial tissue producing COLLAR BUTTON LESION
  • peripheral tumors are solid and nodular
39
Q

Carcinoids–histologically

A
  • made of organic, trabecular, palisading, ribbon or reset-like arrangements of cells separated by delicate fibrovascular stroma
  • Like GI tract lesions, the cells are regular and have uniform round nuclei and moderate amount of eosinophilic cytoplasm
40
Q

Typical vs. atypical carcinoids morphology

A
  • Typical have fewer than 2 mitosis per 10 HPFs and lack necrosis!
  • Atypical have bw 2-10 mitoses per 10 HPFs and/or foci of necrosis
  • Atypical also show increased pleomorphism, have more prominent nucleoli and grow more disorganizedly and invade lyphatics
41
Q

Electron microscopy of carcinoid tumors

A

-dense core granules characteristic of other neuroendocrine tumors and by immunohistochemistry are found to contain serotonin, neuron specific enolase, bombesin, calcitonin, other peptides

42
Q

Clinical features of bronchial carcinoid tumors

A
  • bronchial carcinoids arise from their intraluminal growth, capacity to metastasize and ability of some to elaborate vasoactive amines
  • persistent cough, hemoptysis, impaired drainage of resp passages with secondary infections, bronchiectasis, emphysema, and atelectasis
43
Q

Carcinoid syndrome

A

-intermittent attacks of diarrhea, flushing, and cyanosis

44
Q

Bronchial Carcinoid tumors prognosis

A
  • Most bronchial carcinoids do not have secretory activity and do not metastasize so follow benign course for long periods and are amenable to resection
  • high 5yr survival rate for typical carcinoids, 70% for atypical, 3-% for large cell neuroendocrine carcinoma and 5% for small cell carcinoma
45
Q

Miscellaneous tumors

A
  • benign and malignant mesenchymal tumors like:
  • inflammatory myofibroblastic tumor, fibroma, fibrosarcoma, lymphangieleiomyomatosis, leiomyoma, leiomyosarcoma, lipoma, hemangioma, chondroma,
  • benign and malignant hematopoietic tumors may also affect lungs usually as part of generalized disorder–include: Langerhans cell histiocytosis, non Hodgkin and Hodgkin lymphomas, lymphomatous granulomatosis, unusual EBV positive B cell lymphoma, low grade extra nodal marginal zone B cell lymphoma
46
Q

Lung hemartoma

A
  • common, incidental fining–rounded radio-opacity (coin-lesion) on routine chest film
  • Most are solitary, less than 3-4 cm in diameter and well circumscribed
47
Q

Pulmonary hemartoma consists of

A
  • nodules of connective tissue intersected by epithelial clefts
  • cartilage is the most common connective tissue but there may also be cellular fibrous tissue and fat
  • epithelial clefts are lined by ciliated columnar epithelium or nonciliated epithelium and represent entrapment of resp epithelium
48
Q

Hemartoma–genetic abnormality

A

-clonal neoplasm associated with chromosomal aberrations involving either 6p21 or 12q14-q15

49
Q

Lymphangioleiomyomatosis

A
  • pulmonary disorder that primarily affects young woman of childbearing age
  • proliferation of perivascular epithelioid cells that express markers of both melanocytes and smooth muscle cells
  • proliferation distorts involved lung leading to cystic, emphysema like dilation of terminal airspaces, thickening of airspaces, thickening of interstitium, obstruction of lymphatic vessels
  • LoF mutations in tumor suppressor TSC2!!
50
Q

TSC2

A
  • encodes the protein tubers which is a negative regulator of mTOR which regulates cellular metabolism
  • TSC2 mutations–>increased mTOR activity
  • since Lymphangioleiomyomatosis commonly affects young women, thought that estrogen contributes to proliferation of perivascular epithelioid cells which have estrogen receptors
51
Q

Lymphangioleiomyomatosis–common presentation, prognosis and treatment

A
  • Dyspnea or spontaneous pneumothorax (related to emphysematous changes)
  • slowly progressive over several decades
  • mTOR inhibitors being tested but currently only definitive treatment is lung transplantation
52
Q

Inflammatory myofibroblastic tumor

A
  • rare; more common in children with equal M/F ratio
  • Fever, cough, chest pain and hemoptysis
  • May also be asymptomatic
  • Imaging shows single round, well-defined, peripheral mass with calcium deposits
  • lesion is firm, 3-10 cm in diameter and grayish white
53
Q

Inflammatory myofibroblastic tumor–microscopically and Tx

A
  • proliferation of spindle-shaped fibroblasts and myofibroblasts, lymphocytes, plasma cells and peripheral fibrosis
  • some have rearrangements of ALK gene, on 2p23
  • Tx=sustained responses in
54
Q

Tumors in mediastinum arise where?

A
  • mediastinum or may be metastatic from the lung or other organs
  • may also invade/compress lungs

Respiratory Medicine Midterm (17 decks)

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