Pulmonary Path II
lots of neoplasia
December 10, 2008
Case I: 62-year old woman with productive cough, fever,
chills, and pleuritic chest pain.
A 62 year-old woman develops cough productive of green sputum, dyspnea, fever, chills, and
pleuritic chest pain. She had a “cold” (stuffy nose, sneezing, sore throat) for the past week. Her
past history is negative for any hospitalization or surgery. On exam her temperature is 101F.
Oxygen saturation on room air is 89%. On percussion there is dullness over the right upper lung
field. On auscultation there are bronchial breath sounds in the right upper lung field.
*Sputum gram stain shows few squamous cells, many neutrophils, and Gram positive diplo-cocci.
Overall Case Analysis & Notes:
We are thinking of something infectious due to fever, chills
Get a sputum sample (should not see squamous cells really), chest x-ray
See consolidation on CXR
Case I: 62-year old woman with productive cough, fever,
chills, and pleuritic chest pain.
a.
Identify organ: Lung
b.
Diagnosis: Community-Acquired Pneumonia (MC Strep Pneumo, accounts for 90% of cases of “lobar”
pneumonia); also H. Influ, Moraxella Cat (elderly), Staph aureus (IntraVenousDrugsUers), Legionella,
Enterbacteriaceae
c.
Describe the characteristic pathologic changes in the specimen. See histology slide—see alveoli with WBC’s,
engorged with fluid
c. Correlate the clinical findings with the pathology.
Fever and chills—acute inflammation (cytokines); Purulent sputum---bronchiolitis; chest pain---pleuritis; recent
(likely viral) URI that impaired mucociliary apparatus/pulmonary defense mechanism
Complications can include: abscess, empyema, bacteremia
Case I: 62-year old
woman with
productive cough,
fever, chills, and
pleuritic chest pain.
1. Congestion
1. Red hepatization
1. Gray hepatization
1. Resolution
Bronchopneumonia
Note the large and small yellow-tan patches (arrows)
of pneumonia scattered throughout lung.
Case I: 62-year old woman
with productive cough,
fever, chills, and pleuritic
chest pain.
Bronchopneumonia=“patchy”
consolidation
Lobar pneumonia-consolidation
of a large portion of lobe or
whole lobe
Bronchopneumonia
The cut surface of the lung reveals large and small, yellow-tan patches (arrows)
of pneumonia scattered throughout the lung.
Case I: 62-year old
woman with
productive cough,
fever, chills, and
pleuritic chest pain.
Lobar Pneumonia
The "gray hepatization" stops abruptly at the fissure.
Case I: 62-year old woman with productive cough, fever,
chills, and pleuritic chest pain.
Remember for Zoomify:
1.What tissue is it? (alveoli, lung)
1.What is in the alveoli?
(neutrophils, lymphocytes, fluid)
1.See areas of fibrin deposition
1.Bronchi have inflammatory cells
1.Pleura has inflammatory cells and
is edematous
alveoli filled with neutrophils
alveoli delineated by engorged septal capillaries
Case II: 57 y/o man smoker; hemoptysis
•
57-year-old man develops hemoptysis. He has been smoking two packs of cigarettes per day for
30 years. He has had a chronic cough worse in the morning for 10 years. He has had mild dyspnea
on exertion in the past 5 years
Overall Case Analysis & Notes:
DDx: chronic bronchitis, klebsiella pneumonia (rusty sputum), neoplasia
What now? CXR, culture sputum
we see on CXR: upper lobe cavitating mass where you can see air fluid levels in the cavity; could be
cancer, pneumonia, or TB; thick wall around the mass
We would probably also get a CT, bronchoscopy (run a tube/scope down into lung to take a look)
Case II: 57 y/o man smoker; hemoptysis
Squamous cell carcinoma of the lung
a. Identify organ: lung Diagnosis: squamous cell
b. Describe the characteristic pathologic changes in the specimen.
Keratin pearls + intercellular bridgessquamous cell carcinoma of the lung
c. Correlate the clinical findings with the pathology.
•
Smoking history; origin is central bronchi, grows faster than other bronchogenic cancers (small cell,
adenocarcinoma) and mets happen later; precursor lesions are bronchial epithelial squamous metaplasia,
dysplasia, carcinoma in situ
•
note that you don’t do surgery on small cell carcinoma—send to oncology
•
Normal epithelium is ciliated columnar, squamous metaplasia to protect self can lead to dysplasia and advance to cancer!
e. What is the most common etiology of this disorder?
f. What underlying genetic disorder(s) can contribute to this disorder?
Cavitation in lft upper lobe;
Could be an abscess, granuloma, mass
Bronchogenic carcinoma
The opened bronchus contains a carcinoma (arrow).
The neoplasm infiltrates adjacent lung (A) and obstructs the lumen, causing
retention of secretions distal to the obstruction.
Nests of neoplastic squamous cells, cells are
Different sizes (pleomorphic)
Mitoses
Keratinization/keratin pearlsSquamous cell carcinoma
Also see intercellular bridges
Case III: 69-year-old woman with a “coin lesion” in the
periphery of the right lung on x-ray: Adenocarcinoma
•
69-year-old woman presents to the emergency room with chest pain. She has no chronic medical
problems. She smoked 1 pack of cigarettes during her first two years of college, none since. On
physical exam heart, lung, abdominal exams are normal. On chest X-ray there is a “coin lesion” in
the periphery of the right lung.
Overall Case Analysis & Notes:
Normal Ddx: neoplasia, granuloma, infection, etc.
Case III: 69-year-old woman with a “coin lesion” in the periphery of the
right lung on x-ray: Adenocarcinoma
a.
Identify organ: lung
Diagnosis: adenocarcinoma (see glands on histology slide); there should not be glands in lung like that
b. Describe the characteristic pathologic changes in the specimen.
c. Correlate the clinical findings with the pathology.
•
Lung tissue is replaced by an infiltrating adenocarcinoma which forms glands.
e. What is the most common etiology of this disorder?
•
Most common lung cancer to arise in women and NON-SMOKERS; but can also be found in smokers;
are smaller, peripherally located
•
5 year survival is about 10%
f. What underlying genetic disorder(s) can contribute to this disorder?
Coin Lesion (R field)
Adenocarcinoma b/c
of glandular
formation
Malignant cells forming glands
Case IV: 51-year-old woman with cough productive of graywhite mucous. Chest x-ray shows a diffuse infiltrate in the
periphery of the right lower lobe.
•
51-year-old-woman complains of cough for several weeks. The cough is productive of gray white
mucous material. She has never smoked. On physical exam there are decreased breath sounds in
the lower right lung field. Chest X-ray shows a diffuse infiltrate in periphery of the right lower
lobe.
Overall Case Analysis & Notes:
•
Pneumonia (diffuse); Neoplasia, Miliary Tuberculosis (PPD purified protein derivative)
•
Ask about recent infection, if fever, fatigued
-----------------------------Miliary tuberculosis (or disseminated TB) is a form of tuberculosis that is characterized by a wide dissemination into
the human body and by the tiny size of the lesions (1-5 mm). Its name comes from a distinctive pattern seen on a
chest X-ray of many tiny spots distributed throughout the lung fields with the appearance similar to millet seeds,
thus the term "miliary" tuberculosis. Miliary TB may infect any number of organs including the lungs, liver, and
spleen.
Case IV: 51-year-old woman with cough productive of gray-white
mucous. Chest x-ray shows a diffuse infiltrate in the periphery of the
right lower lobe.
Identify organ: lung & Diagnosis: BRONCHIOALVEOLAR carcinoma, a subtype of adenocarcinoma
b. Describe the characteristic pathologic changes in the specimen.
Alveolar walls are thickened; hypercellularity; alveoli are filled with desquamated cells and Mphages; large
neoplastic cells have abundant cytoplasm and prominent vesicular nuclei
c. Correlate the clinical findings with the pathology.
e. What is the most common etiology of this disorder?
Arises from terminal bronchioles or alveolar walls; grossly—multiple diffuse nodules (pneumonia-like
consolidation); involves males and females;
Multiple presentations on Xray like multicentric acinar nodules; solitary pulmonary nodule, alveolar cell
carcinoma that looks like pneumonia
Alveoli lined by large neoplastic cells
Normal alveoli
Desquamated neoplastic cell
Alveoli lined by large neoplastic cells
with abundant cytoplasm
Case V: 71 year-old man with back pain, hepatomegaly, and
enlarged hilar lymph nodes
•
A-71 year-old man develops progressive chest pain, dyspnea and back pain. He has had a 20 pound
unintentional weight loss over 3 months. He smokes and has a 50 pack year smoking history. On
physical exam there is hepatomegaly. Chest X-ray shows enlarged hilar and mediastinal lymph
nodes. CT scan shows bilaterally enlarged adrenal glands and multiple masses in the liver.
•
Overall Case Analysis & Notes:
•
20 pound unintentional weight loss; smoking 50 pack-year historyworried about cancer
•
Enlarged hilar and mediastinal lymph nodes support diagnoses of sarcoid and cancer
•
Bilateral enlarged adrenals and masses in liver support diagnoses of cancer
Case V: 71 year-old man with back pain, hepatomegaly, and enlarged
hilar lymph nodes: Bronchiogenic Small Cell Carcinoma
a. Identify organ:
Diagnosis:
b. Describe the characteristic pathologic changes in the specimen.
Nests of small round/oval cells with scant cytoplasmsmall cell carcinoma (cells 2 to 3x as big as lymphocytes)
Neoplasm penetrates the bronchial wall, lying adjacent to strips of hyaline cartilage
c. Correlate the clinical findings with the pathology.
Smoking=risk factor; hilar or central location, mets are wide, sensitive to chemo but invariably recure, ectopic
hormone production may lead to development of paraneoplastic syndomes
remember ACTH with small cell
e. What is the most common etiology of this disorder?
f. What underlying genetic disorder(s) can contribute to this disorder?
Case V: 71 year-old
man with back pain,
hepatomegaly, and
enlarged hilar lymph
nodes
Bronchogenic carcinoma
The right lung is bisected into an anterior half (A) and a posterior half (B).
The white neoplasm occupies most of the lower lobe and extends into upper lobe.
The neoplasm obstructs the right mainstem bronchus.
Peribronchial lymph nodes (arrow) contain neoplasm.
Centrally located
Case V: 71 year-old
man with back pain,
hepatomegaly, and
enlarged hilar lymph
nodes
Neoplasm is composed of small cells containing dark blue, round nuclei and
sparse cytoplasm.
These cells resemble (but are not) lymphocytes and are arranged in clusters
Case V: 71 year-old
man with back pain,
hepatomegaly, and
enlarged hilar lymph
nodes
Metastatic Carcinoma
Liver parenchyma (cut surface) largely replaced
by metastastic carcinoma (yellow arrow)
Multiple lobules on liver
Genetic mutations in
cancer
• Dominant oncogene abnormalities (protooncogene)
• C-myc overexpression (small cell)
• K-Ras mutations (adenocarcinomas)
• Recessive Oncogene (tumor suppressor gene)
•
•
•
•
P53 mutations
Rb gene mutations
3p deletions
EGFR mutation
So What?
• Molecular epidemiology: genetic stratification of lung cancer risk
• Early detection-specific molecular changes in sputum, blood, bronchial
biopsies, brushings, lavage specimens
• Chemoprevention
• Diagnosis to help with subtype differentiation
• Treatment-direct towards molecular targets to get selectivity for the lung
cancer and not normal tissue
• Prognosis-survival, met potential, probability cancer will respond to chemo