Lung Adenocarcinoma Classification
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Direct answer
A ground-glass nodule on CT is adenocarcinoma biology made visible: the same spectrum that radiologists watch runs from atypical adenomatous hyperplasia through adenocarcinoma in situ (3 cm or less, pure lepidic growth, essentially 100% five-year survival) and minimally invasive adenocarcinoma (invasion 5 mm or less) to invasive adenocarcinoma with five classical patterns — lepidic, acinar, papillary, micropapillary and solid with mucin. The IASLC grading system, adopted into WHO 2022, converts pattern percentages into grades 1-3, with 20% or more high-grade patterns (solid, micropapillary, complex glandular) defining grade 3. Spread through air spaces (STAS) is the newest prognostic concept, and "BAC" is a retired term no report should contain.
What you must remember
- The precursor ladder: atypical adenomatous hyperplasia (mildly atypical cells lining alveoli), AIS (3 cm or less, pure lepidic, no stromal invasion), MIA (3 cm or less, lepidic with invasion 5 mm or less, no lymphovascular or pleural involvement) — AIS and MIA carry essentially 100% five-year survival after resection.
- The five patterns of invasive adenocarcinoma: lepidic (tumour along alveolar walls), acinar, papillary, micropapillary (worst prognosis, even in small percentages) and solid with mucin; the report records each pattern in 5% increments.
- IASLC/WHO 2022 grading: grade 1 — lepidic, acinar or papillary only; grade 2 — acinar or papillary with under 20% high-grade patterns; grade 3 — 20% or more high-grade patterns (solid, micropapillary, complex glandular/cribriform/fused).
- Variants: invasive mucinous adenocarcinoma (former mucinous BAC — columnar goblet cells, KRAS-enriched, often multifocal, TTF-1 negative with CK7+/CK20+), colloid, fetal and enteric adenocarcinoma.
- STAS: tumour cells floating within air spaces beyond the tumour edge — a form of invasion-associated spread predicting recurrence, particularly relevant in sublobar resections.
- Immunohistochemistry: TTF-1 and Napsin A support pulmonary adenocarcinoma; p40 (and p63) supports squamous; mucinous adenocarcinoma may be TTF-1 negative.
- Management anchor: lobectomy with systematic nodal dissection remains standard; sublobar resection is considered for small peripheral tumours, where AIS/MIA status and STAS negativity matter most.
Percentaging a resection, then grading it
A lobectomy specimen contains a 2.5 cm non-mucinous adenocarcinoma. The pathologist maps the histology slide by slide: 60% acinar, 25% papillary, 15% micropapillary. Pattern arithmetic first — high-grade patterns (micropapillary here) total 15%, below the 20% threshold, so the tumour is grade 2 despite containing the worst pattern. Add STAS assessment at the tumour edge: nests of tumour cells floating in air spaces beyond the main mass would upgrade the concern and argue against any wedge resection strategy, since the aerial spread is invisible to the surgeon's palpation. The final report couples the grade with molecular testing — EGFR, ALK, ROS1 and beyond — because pattern and genotype travel together imperfectly: solid pattern with signet-ring cells raises TTF-1 retention and ALK fusions, while the mucinous variant runs on KRAS and may be multicentric. One resection, four reportable dimensions: pattern percentages, grade, STAS, genotype.
Where students slip
The retired term "bronchioloalveolar carcinoma" is the first trap — it merged AIS, MIA and the mucinous variants under one obsolete name, and using it dates a report and an answer. The second slip is pattern arithmetic: 19% micropapillary is grade 2, 21% is grade 3, and examiners set the number deliberately around the threshold. Third, micropapillary presence matters even below 5% in clinical decision-making, so the grade must not lull anyone. Mucinous adenocarcinoma is the phenotype trap — TTF-1 negative, CK20 positive, multifocal, KRAS-driven — easily misread as metastatic gastrointestinal adenocarcinoma without clinicopathological correlation. In vivas, the survival contrast between AIS (essentially 100%) and invasive grade 3 disease frames why frozen-section assessment of ground-glass nodules changed surgical practice.
Frequently asked questions
What defines minimally invasive adenocarcinoma?
A lepidic-predominant tumour of 3 cm or less with invasive component 5 mm or less, and no lymphovascular, pleural or necrotic features — near-100% five-year survival.
Which pattern carries the worst prognosis?
Micropapillary, even in small percentages; solid and complex glandular patterns share high-grade status.
How is IASLC grade 3 defined?
High-grade patterns — solid, micropapillary, complex glandular — occupying 20% or more of the tumour.
What happened to the term BAC?
It is retired: the entities it lumped together are now AIS, MIA, lepidic-predominant and invasive mucinous adenocarcinoma.
Which markers distinguish invasive mucinous adenocarcinoma?
TTF-1 negativity with CK7 and CK20 positivity, goblet-cell morphology and KRAS-enriched genetics, often with multifocal disease.