Molavi Chapter 22 - Lungs and Pleura Flashcards
Movat’s stain
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.
Pulmonary adenocarcinoma-in-situ
Malignant cells line alveolar walls, but do not invade the stroma
Pulmonary squamous cell carcinoma
- Arises from squamous metaplasia, often in the major bronchi and therefore more centrally
- May be keratinizing, non-keratinizing, or basaloid
Squamous cell carcinoma of the lung variants
Staining of squamous cell carcinoma of the lung
All should be p40+, a marker of squamous differentiation
This is especially helpful for identifying non-keratinizing squamous cell tumors
Pulmonary adenocarcinoma
- 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)
Staining of adenocarcinoma of the lung
- 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
Large cell carcinoma
- Basically a non-small cell carcinoma with no recognizable gandular or squamous features
- Old, now outdated term
Spindle cell or sarcomatoid carcinoma of the lung
- 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
Pleomorphic carcinoma
Used to describe combined tumors in which there is a recognizable conventional carcinoma (adeno or squamous) plus a spindle cell or giant cell component.
Typical carcinoid tumor
- 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
Atypical carcinoid tumor
Differentiated by increased mitotic rate (2-10 per 2mm2) or by necrosis.
More aggressive behavior.
Usually >10% Ki67
Small cell carcinoma of the lung
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
Stains for neuroendocrine origin
- Synaptophysin
- Chromogranin
- CD56
Lung cancer staging
Lung cancer lymph node drainage pathway
Bronchial lymph node numbering
The reserve cells of alveoli are ___.
The reserve cells of bronchi are ___.
The reserve cells of alveoli are type II pneumocytes.
The reserve cells of bronchi are clara cells (club cells).
What’s going on in this alveolus?
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.
In the lung, arteries follow ___, veins follow ___.
In the lung, arteries follow bronchi, veins follow septa.
Diffuse alveolar damage
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
Acute bronchopneumonia
Neutrophilic inflammation of alveoli (neutrophilic alveolitis)
Also w/ nonspecific findings of acute injury
Organizing pneumonia
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.
Constrictive bronchiolitis
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).
Nonspecific interstitial pneumonia
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.
Usual interstitial pneumonia
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.
Umbrella term “interstitial lung disease”
- Includes six histologic patterns:
-
Two are acute/subacute:
- Acute interstitial pneumonia
- Constrictive bronchioloitis
-
Two are chronic:
- Idiopathic pulmonary fibrosis
- Nonspecific interstitial fibrosis
-
Two are smoking-related:
- Desquamative interstitial pneumonia
- Respiratory bronchiolitis - interstitial lung disease
-
Two are acute/subacute:
IgE-mediated allergic lung disease
- Asthma,
- allergic bronchopulmonary aspergillosis,
- bronchocentric granulomatosis,
- eosinophilic pneumonia
Cell-mediated hypersensitivity allergic lung disease
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:
- patchy interstitial chronic inflammation
- poorly formed small non-necrotizing granulomas
- organizing pneumonia
Lung diseases of smokers
-
Interstitial:
- Desquamative interstitial pneumonitis
- Respiratory bronchiolitis
- Langerhans cell histiocytosis
-
Obstructive:
- Empyhsema
- Chronic bronchiolitis
Respiratory bronchiolitis
An interstitial lung disease of smokers
Increase in pigmented macrophages within alveolar (and bronchial) spaces
Desquamative interstitial pneumonitis
An interstitial lung disease of smokers
More extreme presentation than respiratory bronchiolitis. Macrophages pack the alveoli.
Langerhans cell histiocytosis
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.
Hamartoma
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.
Pulmonary blastoma
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
Types of mesothelioma
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.
What are the next steps if you think a tumor is neuroendocrine?
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.
