Definition
A malignant epithelial tumour with glandular differentiation or mucin production.
Adenocarcinoma accounts for about 28% of primary lung carcinomas in men, 42% in women, and represents an increasing proportion of lung cancers2. Although most cases occur in smokers, with a relative risk of 4.1 for heavy smokers12, adenocarcinoma is the most common primary pulmonary malignancy in non-smokers.
Tumours tend to be peripheral and under 4 cm in size. There is a relatively high frequency of pleural involvement. Cavitation is rare. None-solid or part-solid nodules are more likely to be malignant and are more often bronchoalveolar carcinomas or adenocarcinomas with bronchoalveolar features11. For radiological prognostic factors, see below. Pure bronchoalveolar carcinomas can be differentiated as pure ground glass opacities devoid of lymphangitis23; the contrast index may help to identify BAC25.
Bronchoalveolar carcinoma often shows aerogenous spread within the same or other lobes.
Most adenocarcinomas show a mix of subtypes and degrees of differentiation.
Subtypes: acinar, papillary (including micropapillary) , bronchoalveolar, solid with mucin production. The solid variant requires mucin to be present in at least five tumour cells in each of two high power fields on mucin staining. Papillary tumours may be predominantly endobronchial15. Papillary carcinomas fill distort or replace alveolar spaces, show marked nuclear atypia, commonly contain psammoma bodies, in contrast to bronchoalveolar carcinoma29.
Variants:
Bronchoalveolar carcinoma (BAC) shows lepidic spread along alveolar structures without stromal, vascular or pleural invasion. Sclerosis produces septal widening. BAC may be mucinous or non-mucinous. (The requirement of the WHO for no invasive component is an over-stringent definition. The WHO lists BAC as a subtype rather than a variant, but the requirement for no invasion makes no sense unless it is being applied to a pure variant. Localised BAC without fibroblastic proliferation has been reported to be associated with a lack of lymph node micrometastases13. In two studies, BAC associated with an invasive component not more than 5 mm in diameter has low rates of vascular, lymphatic and pleural invasion and does not show lymph node metastases20,32. A minimal invasive component is compatible with an excellent prognosis: see below.)
Clear cell adenocarcinoma: needs to be differentiated from other tumours that may be composed predominantly of clear cells; primary large cell carcinoma, primary squamous cell carcinoma and metastatic renal cell carcinoma.
Adenocarcinoma with rhabdoid features3.
See immunohistochemistry of malignant epithelial tumours of lung.
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positive in 75% of cases |
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positive |
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positive |
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usually positive |
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usually negative |
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positive |
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positive |
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negative |
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Transcription factor E2F1 |
1/1135 |
Mucinous BAC is often negative for TTF-1 and positive for CK20. See mucinous adenocarcinoma of lung.
Metastatic adenocarcinoma: tend to be more homogenous than do primary tumours. A BAC component favours a primary, but some metastases may show this growth pattern. Except those from the thyroid, metastases are negative for TTF-1.
Prostate: the tumour is often microacinar or cribriform with lymphatic permeation, a lack of stromal response uniform round nuclei with prominent nucleoli and prominent cell borders, as well as positive for prostate specific antigen and prostatic acid phosphatase10. Metastatic prostatic duct carcinoma resembles colonic adenocarcinoma. Other tumours with a solid or nested pattern resemble carcinoids tumour, but lack the stippled nuclear chromatin10.
Breast: positive for steroid receptors ER and PR (as may be primary carcinoma of lung) and GCDFP.
Metastatic thyroid carcinoma is positive for thyroglobulin and lacks mucin.
Atypical alveolar hyperplasia (AAH): non-mucinous broncho-alveolar carcinoma is usually greater than 5 mm in diameter and usually shows marked cellular stratification, micropapillary tufting, high cell density, marked overlapping of nuclei, coarse chromatin and prominent nucleoli. AAH usually shows not more than one of these features.
reactive pneumocyte hyperplasia adjacent to scars and to organising ARDS.
Bronchiolar metaplasia in interstitial pneumonia.
Surgical resection, if possible.
Radiological features: Small tumours (20 mm or less in diameter) which show more than 50% ground glass type opacity are associated with the absence of relapses after resection14. Another study showed improved survival in adenocarcinomas smaller than 15 mm with >57% ground glass opacity31. Small (<20 mm) radiologically air-containing tumours have a lower rate of metastases and better survival than radiologically solid small tumours16.
Adenocarcinomas have a higher rate of recurrence than other non small cell carcinomas, more so if the primary tumour is bigger than 3 cm, there are satellite nodules or nodal metastases9.
Several studies have shown similar results for small peripheral adenocarcinomas:
Localised resected BAC and tumours less than 20 mm in diameter without active fibrosis, with or without invasion, had no nodal metastases or micrometastases13 and 100% 5 year survival18.
In peripheral adenocarcinomas smaller than 30 mm with no or sparse desmoplastic response, the five years survival was 100%17.
For adenocarcinomas 30 mm or less in diameter where the central scar was not more than 5 mm in size, the five year survival was 100%19. A more heavily collagenised scar is associated with a higher incidence of metastases and poorly prognosis28.
For adenocarcinomas not more than 30 mm in diameter, more than 75% lepidic growth, central fibrosis not more than 5 mm in diameter and no destruction of the elastic alveolar framework, were associated with 100% survival21.
Papillary carcinoma needs to be distinguished from bronchoalveolar carcinoma, as having a worse prognosis29.
Bronchoalveolar carcinomas in never-smokers may be more responsive to therapy with gefitinib22.
Positivity for neuroendocrine markers may be an adverse prognostic marker4,5, but may also be associated with increased responsiveness to chemotherapy6.
Gene-expression profiling may provide additional prognostic information7,8,11,24,27,33, as may proteomic patterns34.
Tumours of the Lung, Pleura, Thymus and Heart. WHO Classification of Tumours. IARC Press 2004.
2 Travis WD, Travis LB,Devesa SS Lung cancer. Cancer 1995; 75:191-202
This page last revised 29.4.2005.
©SMUHT/PW Bishop