Adenocarcinoma

Definition

Malignant neoplasm of respiratory epithelium with glandular differentiation and mucin production, and exhibiting acinar, papillary, bronchioloalveolar or solid growth patterns.

Clinical Features

≈50% of all lung carcinomas in females
<50% of all lung carcinomas in males1,2
In absolute numbers, more common in males
May be becoming more prevalent than other microscopic types of lung cancer 3–5

Pathogenesis

Overexpression of p53 tumor suppressor gene product:
- associated with cigarette smoking 6
- very early event in genesis7
K-ras oncogene activation:
- detected in lung adenocarcinomas from former smokers
- suggests that K-ras mutations are an early and irreversible event in development8
- K-ras mutation occurs in atypical bronchioloalveolar hyperplasia9

Gross Pathology

Usually:
- poorly circumscribed
- gray–yellow lesions (Fig. 1
  Fig. 1: Typical peripheral location of pulmonary adenocarcinoma.
  )
Single or multiple10
Mucoid glairy appearance if secrete abundant mucin
Cavitation extremely unusual
≈65% peripheral location
At excision 77% involve visceral pleura:
- often resulting in pleural fibrosis or ‘puckering’ (Figs 2 and 3
  Fig. 2: Outer aspect of pulmonary adenocarcinoma showing pleural retraction.
  Fig. 3: Cut section of pulmonary adenocarcinoma showing pleural retraction.
  )
Occasionally:
- pseudomesotheliomatous carcinoma:
  - both pleural layers coated by a small peripheral adenocarcinoma that has spread massively into pleural space
  - simulates diffuse mesothelioma11–14 (Fig. 4
    Fig. 4: Peripheral adenocarcinoma of lung spreading diffusely to pleural surfaces and closely simulating the gross appearance of malignant mesothelioma. Note metastases in perihilar and intertracheobronchial nodes.
    )
Even rarer:
- presentation as large endobronchial polypoid mass15
High percentage associated with peripheral scar or honeycombing:
- may show foci of atypical bronchiolar and alveolar proliferation in neighboring air spaces16–21
- of 82 ‘scar cancers’:
  - 18% squamous cell carcinomas 22
  - remainder large cell undifferentiated carcinomas
  - no small cell carcinomas
controversy about whether scar:
- precedes carcinoma
- is a desmoplastic host reaction to the tumor
  - immunophenotyping of collagen in scar suggests desmoplastic host reaction is most prevalent mechanism23–26

Histopathology

Wide range of differentiation:
- other extreme blending with undifferentiated large cell carcinoma 27,28
Glandular differentiation:
- two morphologic signs often found together are:
  - secretion of mucin (Fig. 5
    Fig. 5: Well-differentiated adenocarcinoma.
    )
- depending on relative prominence subdivided with considerable overlap into:
  - acinar
  - papillary:
    - controversial relationship with bronchioloalveolar carcinoma
    - sometimes close morphologic similarity with metastatic papillary thyroid carcinoma – both are TTF-1 immunoreactive
  - solid (adeno)carcinomas with mucin production
Lining of tumor cells along alveolar walls:
- a pattern of growth of many primary or metastatic tumor types
- can simulate gland formation
Much rarer:
- pagetoid spread along mucosa of large bronchi29
Occasionally prominent eosinophilic intracytoplasmic globules30
Blood vessel invasion in 86%1
Metastases to peribronchial or hilar lymph nodes in 50%1
Ultrastructurally:
- may be neoplastic counterparts of all major cells lining bronchial tree including:
  - goblet cells
  - mucous cells
  - nonciliated bronchiolar cells
  - Clara cells31–34

Special Stains and Immunohistochemistry

Reactivity for:
- secretory components 35–38
Expression of keratin 7:
- evidence of glandular differentiation 39
Sometimes coexpression of keratin and vimentin40
S-100 protein-positive Langerhans' cells frequent in stroma41
Surfactant apoprotein (PE-10) positivity:
- ≈50%
- useful in differential diagnosis with:
  - other types of primary lung carcinoma
  - metastatic adenocarcinoma42,43
Cathepsin B and basement membrane components also encountered 44
Consistent expression of Lewis X and Y blood group antigens:
- may be of some differential diagnostic value45,46

Diagnosis

Rare Variants

Signet ring adenocarcinoma 47,48 (Fig. 6
Fig. 6: Primary pulmonary adenocarcinoma with signet ring cells, a most unusual finding in this location.
)
Mucinous carcinoma49
Adenocarcinoma with enteric (goblet cell)12,50 and hepatoid differentiation 51,52
Adenocarcinoma with choriocarcinomatous foci 53

Differential Diagnosis

Select up to 2 differential diagnoses to compare with Adenocarcinoma

Management

Resectability rate 71%:1
- about twice overall rate for lung carcinoma

Prognosis

Poor prognosis may be associated with:
- predominantly micropapillary of growth54,55
- K-ras mutation 56

References

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Last updated: 5 Apr 2006