Molavi Chapter 22 - Lungs and Pleura

Question 1

Movat’s stain

Answer 1

Standard supplemental stain for non-neoplastic lung

Pentachrome stain that highlights elastic laminae as black, hyaluronic acid or mucin as aqua blue, mature collagen as yellow, smooth muscle as dull red, fibrinoid necrosis (in vessels) as bright red.

Makes finding fibroblastic foci easy in cases of organizing pneumonia.

Question 2

Pulmonary adenocarcinoma-in-situ

Answer 2

Malignant cells line alveolar walls, but do not invade the stroma

Question 3

Pulmonary squamous cell carcinoma

Answer 3

• Arises from squamous metaplasia, often in the major bronchi and therefore more centrally
• May be keratinizing, non-keratinizing, or basaloid

Question 4

Squamous cell carcinoma of the lung variants

Answer 4

Question 5

Staining of squamous cell carcinoma of the lung

Answer 5

All should be p40+, a marker of squamous differentiation

This is especially helpful for identifying non-keratinizing squamous cell tumors

Question 6

Pulmonary adenocarcinoma

Answer 6

• Glandular or mucinous [F] (mostly goblet cell-like) differentiation
• Prorgresses along: AIS (predominantly in-situ with <5 mm stromal invasion), minimally-invasive (< 3cm stromal invasion), or invasive.
• Sub-patterns:
  
  • Acinar [C]
  • Lepidic [A] (growing along alveolar walls)
  • Solid [D]
  • Papillary [B]
  • Micropapillary [E]
  • Colloid (pools of mucin and floating tumor cells)

Question 7

Staining of adenocarcinoma of the lung

Answer 7

• Most will stain with TTF-1
• Additionally, it is subclassified by presence or absence of mutations in:
  
  • KRAS, EGFR, ALK
• . . . and less commonly:
  
  • HER2, BRAF, PIK3CA, AKT1, MAP2K1, NRAS, ROS1

Question 8

Large cell carcinoma

Answer 8

• Basically a non-small cell carcinoma with no recognizable gandular or squamous features
• Old, now outdated term

Question 9

Spindle cell or sarcomatoid carcinoma of the lung

Answer 9

• Tumor that mimics the stroma, but is demonstrably keratin positive (however this may be sparse and weakly staining)
• Remember: sarcomas often do not have prominent nucleoli, but sarcomatoid tumors do

Question 10

Pleomorphic carcinoma

Answer 10

Used to describe combined tumors in which there is a recognizable conventional carcinoma (adeno or squamous) plus a spindle cell or giant cell component.

Question 11

Typical carcinoid tumor

Answer 11

• Well-differentiated (but not benign) neplasm with classic neuroendocrine features (epithelial-to-spindled architecture, regular round or oval nuclei with speckled salt and pepper chromatin, low mitotic rate, no nucleolus)
• Architecture may be rosette or nested trabecular pattern
• Usually <5% Ki67

Question 12

Atypical carcinoid tumor

Answer 12

Differentiated by increased mitotic rate (2-10 per 2mm²) or by necrosis.

More aggressive behavior.

Usually >10% Ki67

Question 13

Small cell carcinoma of the lung

Answer 13

High-grade neuroendocrine neoplasm with small cell morphology (hyperchromatic, dense indigo-blue nuclei, no nucleoli, syncytial appearance with nuclear molding, frequent mitoses, apoptosis/necrosis, and streaming crush artifact).

High Ki-67 proliferation index

Question 14

Stains for neuroendocrine origin

Answer 14

• Synaptophysin
• Chromogranin
• CD56

Question 15

Lung cancer staging

Answer 15

Question 16

Lung cancer lymph node drainage pathway

Answer 16

Question 17

Bronchial lymph node numbering

Answer 17

Question 18

The reserve cells of alveoli are ___.

The reserve cells of bronchi are ___.

Answer 18

The reserve cells of alveoli are type II pneumocytes.

The reserve cells of bronchi are clara cells (club cells).

Question 19

What’s going on in this alveolus?

Answer 19

Is that a tiny focus of adenocarcinoma? No!!!

Look closely. Those are type II pneumocytes. This is type II hyperplasia, when type II pneumocytes respond to a stressor/loss of type I pneumocytes and must proliferate to fill the space. This is often indicative of chronic inflammation or a repairative response.

Subsequently, they will undergo a transition to become type I-like cells.

Question 20

In the lung, arteries follow ___, veins follow ___.

Answer 20

In the lung, arteries follow bronchi, veins follow septa.

Question 21

Diffuse alveolar damage

Answer 21

Pathologic correlate of ARDS

When there is no identifiable cause, the diagnosis is “acute interstitial pneumonia”

Note that the alveolar spaces are full of blood and fluid

Characteristics: interstitial edema and hemorrhage, hyaline membranes, type II hyperplasia, fibrin thrombi, fibrin extrvasation into alveolar spaces

Question 22

Acute bronchopneumonia

Answer 22

Neutrophilic inflammation of alveoli (neutrophilic alveolitis)

Also w/ nonspecific findings of acute injury

Question 23

Organizing pneumonia

Answer 23

Can represent simply the healing phase of nearly any lung injury, or it can be primary and lead to fibrosis. If idiopathic, it is a cryptogenic organizing pneumonia.

You cannot really assess this without knowing the clinical context.

Fibroblastic foci are the classic finding. They are turquoise on Movat’s stain.

Question 24

Constrictive bronchiolitis

Answer 24

Term that includes both obliterative bronchiolitis (seen in lung transplant rejection) and bronchiolitis obliterans syndrome (in GVHD or chemical injury – popcorn lung due to those exposed in popcorn factories).

Question 25

Nonspecific interstitial pneumonia

Answer 25

Histologic pattern that can be seen in **chronic or repetitive lung injury**. In contrast to usual interstitial pneumonia, NSIP is **temporally and spatially uniform**. Instead of a chaotic remodeling mess in UIP, NSIP is a **diffuse, even thickening** and fibrosis of alveolar walls and septa. Inflammation may or may not be present. **Fibroblastic foci should be absent.** If idiopathic, it is simply **idiopathic NSIP.**

Question 26

Usual interstitial pneumonia

Answer 26

Histologic pattern that can be seen in **chronic or repetitive lung injury**. If idiopathic, it is **idiopathic pulmonary fibrosis.** Like multiple sclerosis, IPF should be both **temporally and spatially heterogeneous**, but evidence of this may be captured in a single biopsy (lesions in multiple places in multiple stages of disease -- acute, subacute, chronic, uninvolved). Characteristics: Prominent **interstitial fibrosis,** **fibroblastic foci** (unlike in organizing pneumonia, involve the primary interstitium rather than airspaces), and **plump, reactive-looking type II pneumocytes.**

Question 27

Umbrella term "interstitial lung disease"

Answer 27

* Includes six histologic patterns: * **Two are acute/subacute:** 1. Acute interstitial pneumonia 2. Constrictive bronchioloitis * **Two are chronic:** 1. Idiopathic pulmonary fibrosis 2. Nonspecific interstitial fibrosis * **Two are smoking-related:** 1. Desquamative interstitial pneumonia 2. Respiratory bronchiolitis - interstitial lung disease

Question 28

IgE-mediated allergic lung disease

Answer 28

1. Asthma, 2. allergic bronchopulmonary aspergillosis, 3. bronchocentric granulomatosis, 4. eosinophilic pneumonia

Question 29

Cell-mediated hypersensitivity allergic lung disease

Answer 29

**Hypersensitivity pneumonia** (aka extrinsic allergic alveolitis) Includes all the **"dirty-job" lung diseases** and the **"[insert exotic pet] fancier's" diseases**. Chronically, any of these can progress to **either UIP or NSIP.** * Histologic triad: 1. **patchy interstitial chronic inflammation** 2. poorly formed small **non-necrotizing granulomas** 3. **organizing pneumonia**

Question 30

Lung diseases of smokers

Answer 30

* **Interstitial:** * Desquamative interstitial pneumonitis * Respiratory bronchiolitis * Langerhans cell histiocytosis * **Obstructive:** * Empyhsema * Chronic bronchiolitis

Question 31

Respiratory bronchiolitis

Answer 31

An interstitial lung disease of smokers Increase in **pigmented macrophages** within **alveolar (and bronchial) spaces**

Question 32

Desquamative interstitial pneumonitis

Answer 32

An interstitial lung disease of smokers More extreme presentation than respiratory bronchiolitis. Macrophages *pack* the alveoli.

Question 33

Langerhans cell histiocytosis

Answer 33

Aka **eosinophilic granuloma** Doesn't have traditional granulomas and may not have eosinophils, so the name is not a lot of help. But, it *does* have collections of **Langerhans cells** (pale nuclei with folds and creases, stains with **S100** and **CD1a**). May occur **systemically in the pediatric** population, but in adults it is an **isolated and reversible pulmonary disease of smokers.**

Question 34

Hamartoma

Answer 34

Tumor-like mass composed of a **disorganized mixture of the normal elements found in that organ.** In the lung, these are often masses of cartilage, fat, smooth muscle, epithelium.

Question 35

Pulmonary blastoma

Answer 35

Form of carcinosarcoma found in adults in which the epithelial component resembles fetal lung and the stromal component may be composed of adult-type sarcomas or immature mesenchymal tissue

Question 36

Types of mesothelioma

Answer 36

Epithelioid (nested, neuroendocrine-like cells) Sarcomatoid (Eosinophilic w/ bands of elastin with intervening mesenchymal cells) Biphasic (Both of the above!) Calretinin helps tease out sarcomatoid component, MOC-31 helps highlight epithelial component.

Question 37

What are the next steps if you think a tumor is neuroendocrine?

Answer 37

Stain w/ chromogranin/synaptophysin to confirm Then, ask the next question: Is this typical or atypical? Look for mitoses, necrosis, Ki67 index. If absent, typical carcinoid. If present, atypical carcinoid.