Back to the Basics!
Immunohistochemistry of adenocarcinoma vs Squamous Lung?
Immunohistochemistry
• Adenocarcinoma of lung - TTF-1 (+), Cytokeratin 7/20 (+/-)
• Squamous of lung - p63 and p40 (+)
Oki now we are going to understand it--
TTF-1 = Thyroid Transcription Factor-1
Nuclear stain, present in:
Primary lung adenocarcinoma
Small cell carcinoma
Thyroid cancers
NOT present in metastatic GI adenocarcinomas → so it confirms lung origin.
→ TTF-1 (+) strongly supports lung primary adenocarcinoma.
CK7 / CK20 profile
These are cytokeratin patterns that help identify tumor origin.
Lung adenocarcinoma pattern:
CK7: positive [7 Lung]
CK20: negative (usually)
Therefore, CK7+/CK20−
Sometimes CK20 may be weakly or focally positive, hence (+/−).
CK20 is normally expressed in:
Gastrointestinal epithelium (colon, stomach, some pancreatic ducts)
Urothelium (bladder)
Merkel cells (skin)
→ CK7+ with TTF-1+ = classic lung adenocarcinoma immunophenotype.
Lung Squamous Cell Carcinoma
p63 (+)
p40 (+)
These are squamous markers.
p63: sensitive but not fully specific (can stain some adenocarcinomas)
p40: the most specific marker for squamous differentiation.
p40 is an isoform of p63 but highly specific to squamous tumors.
→ p40 positivity = strong confirmation of squamous carcinoma of lung.
They are nuclear transcription factor in the p53 family
AdenoSquamous--Mixture of these IHC
Large cell carcinoma will lack these IHC.
T/F
1) Hoarse voice or elevated hemi-diaphragm are usually contraindications.
2) You need FEV 1 > 1.5 L (pre-op) for Lobectomy – FEV 1 > 2 L (pre-op) for Pneumonectomy.
1) True, as it suggests involvement of recurrent L Nerve and phrenic N resp.
2) True, Goal is to have > 40% post-op predicted for FEV-1 (~800ml) and DLCO.
T/F
--> Neo-adjuvant chemo + Pembro followed by surgery and adjuvant Pembro is a standard for patients with stage II-IIIB without EGFR/ALK alterations
True
Which of the statement(s) is false regarding stage 1 tumor?
1) Lobectomy=Wedge resection/segmentectomy stage I tumors < 2 cm, As the lesion becomes closer to 2, the trend favors lobectomy.
2) SBRT is an alternative in high risk patients or those who decline lobectomy
3) Stage 1 tumors are T1-T2a, N0,M0. (≤ 4 cm wo nodes but its okay if its invading visceral pleura/adjacent lobe/main bronchus (upto but not including carina)or associated with obs PNA or atelectasis.
4) Positive surgical margins have poor outcomes.
5) It is NOT standard to offer adjuvant chemo for any stage IA patients. Can be considered for SELECT stage IB patients with features mentioned below, with a modest benefit. There is a clear benefit for stage II/III.
Select high-risk patients-- size >=4poor differentiation, visceral pleural invasion, LVI, high-grade tumor, unknown LN status, non-anatomic wedge resection. For High risk stage 1--5-yr overall survival: No chemo: 56.2% Chemo: 64%
6) No evidence for Carboplatin-based regimen. It has to be a Cisplatin-based therapy.
All are true!!!!
What is category 2A,2B in NCCN?
All recommendations are category __unless otherwise indicated.
Category 1 Based upon high-level evidence (≥1 randomized phase 3 trials or high-quality, robust meta-analyses), there is uniform NCCN consensus (≥85% support of the Panel) that the intervention is appropriate.
Category 2A Based upon lower-level evidence, there is uniform NCCN consensus (≥85% support of the Panel) that the intervention is appropriate.
All recommendations are category 2A unless otherwise indicated.
Category 2B Based upon lower-level evidence, there is NCCN consensus (≥50%, but <85% support of the Panel) that the intervention is appropriate.
Category 3 Based upon any level of evidence, there is major NCCN disagreement that the intervention is appropriate.
TNM Staging.
T1 ≤ 3 [T1a ≤ 1, T1b>1-≤ 2, T1c >2-≤ 3]
T2 >3 but ≤ 5 [T2a >3-≤ 4, T2b <4-≤ 5]
T3 >5 but ≤ 7 or ≤ 7 but invades Parietal pleura, pericardium, chest wall, phrenic Nerve, Azygous vein, thoracic Nerve roots(i.e T1,T2), satellite ganglion or seprate tumor nodule(S) in the same lobe as primary.
T4 > 7 or invades mediastinum (except features listed in T3), thymus, trachea, carina, recurrent L nerve, vagus N, esophagus or diaphragm, heart, major A and V, vertebral bodies, brachial plexis, cervical N roots, seprate tumor nodule(S) in the different ipsilatory lobe as primary.....
N1-Ipsilateral Peribronchial &/or hilar &/or ipsilateral intrapulmonary LNs, including involvement by direct extension.
N2- Ipsilateral Mediastinal LN station(s) &/ subcarinal LN station
N3- Contralateral Mediastinal, Contralateral hilar.
Contralateral or ipsilateral scalene or supraclavicular LN station(s).
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SIMPLIFIED STAGING
Simplified Stage I: LN Negative, < 4 cm in size
Simplified Stage II: Peribronchial or Hilar (N1) LN
Simplified Stage III NSCLC: Mediastinal (N2/N3) LN
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Double-digit like 2R, 4R, 11, 11, 12, 13, 14 are N1 LNs
Single number LN stations are mediastinal, N2 LNs
You can Bx some LNs with EBUS and others with EUS.