adenocarcinoma

Adenocarcinoma has two histologic classifications: 1. bronchial-derived adenocarcinoma, and 2. bronchioloalveolar carcinoma, which is seen in more distal bronchioles and alveolar walls.

Adenocarcinoma is the most common type of bronchogenic carcinoma in women. Unlike squamous cell carcinoma, which is highly correlated with cigarette smoking, adenocarcinoma is the most common bronchogenic carcinoma in nonsmokers. Further contrasts with squamous cell carcinoma are that adenocarcinoma tends to arise more often in peripheral parenchyma and may occur in close relationship to scars (so called "scar cancer"), are smaller in bulk, and grow more slowly than squamous cell carcinoma. Most adenocarcinomas of the lung are actually metastatic in origin, an extrapulmonary primary site should always be excluded before a diagnosis is made of primary pulmonary adenocarcinoma.

This gross image demonstrates the typical location of an adenocarcinoma in relation to an apical scar.

This histologic specimen demonstrates a well-differentiated adenocarcinoma, while this specimen is from lung tissue, adenocarcinomas arising in other sites (breast, prostate, and the GI tract) have similar histopathology. Note the glandular arrangement of the cells, with mucin secreting acini.

This is a cytologic specimen from a case of adenocarcinoma, showing the typical appearance of the cells. Nuclei are rounded with prominent nucleoli, no evidence of keritinization nor prominent intercellular bridges are seen.

Compare the adenocarcinoma cytology with that of a squamous cell carcinoma. Note 2 normal squamous cells in the lower left hand corner, and the keratinizing malignant cells in remainder of the field. The malignant cells show the presence of intercellular bridges, and appear to be forming a keratin pearl.

This is a poorly differentiated adenocarcinoma with loss of acinar structure. Note the anaplasia of the cells, the hyperchromasia of the nuclei, and the infiltration into the lung tissue

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 result are 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

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-Schiff with 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.