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Lung Adenocarcinoma
By Peter C. Fretz, B.S., Jonathan H. Hughes, M.D., PhD

Adenocarcinoma is the most common type of lung cancer, accounting for 30-35% of all cases.Over the past 30 years, the frequency of adenocarcinomas has increased, while, squamous cell carcinomas have decreased.This is believed to be due to a true change in the biological occurence and not a change in criteria for diagnosis. Adenocarcinoma is the most common cause of lung cancer in women and nonsmokers and is the most common cell type associated with lung scarring from other causes ("scar carcinoma").

The majority of adenocarcinomas occur at the periphery of the lung, and, as a resultare often asymptomatic until late in their course. They frequently lie just below the pleura, and cause pleural retraction and thickening on x-ray. Often adenocarcinomas are discovered on routine chest x-rays or in a primary search for distant metastases. Necrosis is uncommon in adenocarcinomas, however, large tumors may show central necrosis and cavitation.Most adenocarcinomas are between 2 and 5 cm at the time of resection.Over half of patients who present with adenocarcinoma are detected by an asymptomatic nodule on a routine chest radiograph.

Gross Appearance

Lung Adenocarcinoma
Adenocarcinoma Picture

Adenocarcinomas grossly present with the "three P's" - peripheral, pigmented and puckered.Commonly lesions are found near the pleural surface (peripheral) which is retracted (puckered) over the neoplasm.The cut surface is often white to pale gray with black anthracotic pigment and glistens if mucin is present. Desmoplastic reactions are often associated with adenocarcinomas and give the tumor a firm fibrous consistency. Adenocarcinomas tend to be well circumscribed and contain central necrotic cores.Less commonly they from cavitary lesions.

Adenocarcinomas are also associated with subpleural scars due to a variety of causes, including old infarcts, healed pneumonitis or granulomas, or trauma.

Microscopic Features

The World Health Organization (WHO) defines adenocarcinoma as "a malignant epithelial tumor with tubular, acinar, or papillary growth patterns, and/or mucus production by the tumor cells."Currently the WHO recognizes four categories of adenocarcinoma:

  • acinar
  • papillary
  • bronchioloalveolar
  • solid carcinoma with mucus formation

However, others have suggested different groupings.

Mucin production is demonstrated by staining with either mucicarmine, periodic acid-Schiffwith diastase (PASD) or Alcian blue.Demonstration of mucin is essential when differentiating the solid variant from a large cell carcinoma of the lung, which by definition stains negatively for mucin.

Adenocarcinomas are also subclassified based upon their degree of differentiation into well, moderate and poorly differentiated forms.This subclassification is based upon the degree of gland formation, regularity of gland architecture, cytologic features, presence of amount of solid areas, level of mitotic activity and the presence and amount of necrosis.Accurate grading also requires an adequate sample, small biopsies tend to be of little value, and initial grades are often changed with more thorough sampling.Histologic grading is not reliable in cases with metastatic disease or following chemotherapy or radiation treatment.Histologic grade tends to correlate poorly with survival data, however, poorly differentiated adenocarcinoma does have a poor prognosis and is rapidly fatal.

The acinar variant is the most common form and is defined by the WHO as having, "a predominance of glandular structures, i.e., acini and tubules with or without papillary or solid areas."The better differentiated tumors form orderly glands lined by tall columnar cells with a regular array of nuclei.

Papillary adenocarcinomas are recognized as having "a predominance of the papillary structures."Papillary architecture begins with the protrusion of cells into the gland lumen.Generally the more well differentiated papillary variants show a core of fibrous connective tissue which is covered by a single layer of uniform cuboidal to columnar cells.Stratification and loss of uniformity are associated with a loss of differentiation.

Bronchoalveolar carcinomas are defined as "an adenocarcinoma in which cylindrical tumor cells grow upon the walls of pre-existing alveoli."(A more thorough discussion of bronchioloalveolar carcinoma is present in the "Bronchioloalveolar carcinoma" section).

Solid carcinomas with mucus formation are recognized as, "poorly differentiated adenocarcinomas lacking acini, tubules and papillae but with mucin containing vacuoles within many tumor cells."Since the solid variant is poorly differentiated by definition, it may be difficult to perceive gland formation. Mucin stains are necessary to demonstrate mucin and differentiate the tumor from a large cell carcinoma.

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