RHS14 - Pulmonary Pathology 7

Question 1

List the types and subtypes of bronchogenic carcinoma we need to know? Why are these distinctions made?

Answer 1

• Non-Small Cell Carcinomas
  
  • Adenocarcinoma
  • Squamous cell carcinoma (SCC)
  • Large cell carcinoma
• Small cell lung carcinoma (SCLC)

Distinctions between SCLC and non-SCLC were made historically because SCLC is quick to metastisize (usually by the time of dx) but responsive to chemo while non-SCLC was the opposite.

Question 2

What is an adenocarcinoma?

Answer 2

A neoplasm of epithelial tissue with glandular origin

Question 3

Describe the progression of lung adenocarcinomas

Answer 3

1. Atypical adenomatous hyperplasia (AAH) - proliferation of minimally atypical pneumocytes along the alveolar septae. Typically found adjacent to the adenocarcinoma
2. Adenocarcinoma in-situ - formation of dysplastic columnar mucin producing cells in the alveolar septae (non-invasive)
3. Minimally invasive adenocarcinoma - invastion < 5mm
4. Invasive

Question 4

Describe the histological appearance of AAH

Answer 4

The epithelium of the alveolus does quite appear to be squamous anymore.

Question 5

Describe the histological appearance of lung adenocarcinoma in situ. What other disease does this look like and how do you tell the difference?

Answer 5

The alveolar epithelium appears to be tall columnar mucin producing cells.

Pneumonia will look similar to this. You’ll know it’s not pneumonia when it is refractory to Abx treatment

Question 6

In what demographic is lung adenocarcinoma most common?

Answer 6

Most common in non-smoking women under the age of 45

Question 7

Describe the growth and metastasis features of lung adenocarcinomas.

Answer 7

In relation to the other non-SCLC, adenocarcinomas typically occur in the periphery of the lung, grow more slowly, but metastasize more quickly (not as quickly as SCLC though). They also often leave behind a scar

Question 8

Describe the histological appearance of invasive lung adenocarcinoma.

Answer 8

You will see glands forming in the lung parenchyma.

Question 9

What are key identifying features of squamous cell carcinoma?

Answer 9

• Occurs centrally near the bronchi
• Higher incidence in men
• Closely aligned with smoking history
• Usually metastasizes to the hilar lymph nodes first
• Often causes airway obstruction leading to atelectasis and/or infection
• Grows fast enough to outgrow its blood supply leading to central necrosis which could eventually cause lung cavitation from the necrotic tumor falling into the airway during coughing

Question 10

Describe the progression of squamous cell carcinoma

Answer 10

1. Squamous metaplasia
2. Squamous dysplasia
3. Squamous cell carcinoma in-situ
4. Invasive squamous cell carcinoma

Question 11

What are the key histological findings to look for to identify squamous cell carcinoma?

Answer 11

• Keratin Pearls - the dysplastic squamous cells secrete and surround a bunch of keratin, forming a pearl appearance
• Intercellular Bridges - bridges connecting the cytoplasm of neighboring squamous cells
• Individual Cell Keratinization - dysplastic squamous cells become laden with keratin, making them very eosinophilic

Question 12

What is large cell carcinoma?

Answer 12

• It is a dianosis of exclusion
• Undifferentiated epithelial malignancy that lacks the features of SCLC and does not possess glandular or squamous differentiation

Question 13

Is the prognosis good or bad for large cell carcinomas? Why?

Answer 13

Poor

The metastasize relatively early and are not very responsive to chemo

Question 14

Describe the histological appearance of large cell carcinoma.

Answer 14

Difficult to precisely describe since diagnosis is mostly based upon what it is not

Cells are usually large, pleomorphic (variable in size, shape, and stain), and bizarrely shaped with no evidence of small cell, squamous cell, or adenocarcinoma features.

Question 15

What are the key identifying features of small cell carcinoma?

Answer 15

• Typicall occur more centrally near the hilum
• Very closely aligned with smoking history
• Metastisizes very early (usually before diagnosis) to the mediastinal lymph nodes
• Responds well to chemo
• Most often the cancer associated with paraneopalstic syndromes

Question 16

What are the key histological findings in small cell carcinoma?

Answer 16

• Cells aren’t actually small, they are:
  
  • Round
  • Scant Cytoplasm (increased nucleus:cytoplasm ratio)
  • Chromatin is finely granulated
  • Nuclear molding (nuclei in the shape of surroundings)
  • Often seen in mitoses
  • Often necrotic
• Cells are fragile and easily destroyed during prep so crush artifacts are often seen

Question 17

Why is neoplasm typing important?

Answer 17

• Cancers that test positive for EGFR mutations (some adenocarcinomas and NSCLCs) respond better to the tyrosine kinase inhibitors gefitinib and erlotinib than patients without the mutation. This is because EGFR is a tyrosine kinase receptor.
• Adenocarcinomas and unspecified NSCLCs usually respond better to pemetrexed than squamous cell carcinomas
• Bevacizumab is contraindicated for squamous cell carcinomas because hemorrhage can occur.
• About half of NSCLCs have an active EML/ALK fusion protein which Crizotinib can inhibit
• KRAS mutation cancers don’t respond well to EGFR inhibitors

Question 18

What is a lung carcinoid?

Answer 18

It is a neuroendocrine tumor of the lung, which arises from Kulchitsky cells (enterochromaffin cells).

Question 19

Where are lung carcinoids usually located and how do they usually grow?

Answer 19

• Basic Characteristics
  
  • Centrally located
  • Polypoid growth (looks like a polyp/mushroom)
  • Usually localized but it can metastasize to lymph nodes

Question 20

What are the clinical features commonly seen with lung carcinoids?

Answer 20

• Patients are usually around 40yo
• Like all centrally located cancers, it can obstruct the airways and lead to atelectasis, cough, hemoptysis, and infection
• These tumors sometimes secrete neuropeptides (usually serotonin) and if they enter into the bloodstream they cause carcinoid syndrome which often present as episodic attack of:
  
  • Vasomotor disturbances (flushes, cyanosis)
  • GIT hypermobility (diarrhea, cramps, vomiting)
  • Asthma attacks

Question 21

Describe the gross and histological appearance of lung carcinoids.

Answer 21

• Gross - small tumorlets that can be polypoid (left image)
• Histology
  
  • Typical - uniformed round cells with “salt & pepper” chromatin situated in nests with no necrosis (right image)
  • Atypical - necrosis is seen

Question 22

What is the typical prognosis for lung carcinoids and why.

Answer 22

Usually a fairly good prognosis because these cancers do not metastasize quickly and are resectable.

Question 23

What areas of the body are affected by malignant mesotheliomas? What are the causes?

Answer 23

• Mesothelioma can occur wherever mesothelial cells are found (serous membranes), but it most often occurs in the lung pleura. It rarely occurs in the peritoneum and pericardium.
• Most common cause is asbestos exposure but sometimes genetic mutation is involved

Question 24

How does malignant mesothelioma appear grossly and on imaging studies?

Answer 24

• Gross - with a thickened and whitened pleura
• Imaging studies show moderate to large unilateral pleural effusion and nodular pleural thickening

Question 25

Discribe the histological appearance of mesothelioma.

Answer 25

Mesothelioma presents with three primary histological patterns

• Epithelioid (left image)
• Sarcomatoid
• Mixed (right image)