pulmonary small cell carcinoma

Digital cases

 JRC:1592 : Small cell carcinoma of the lung.
 JRC:6250 : Small cell carcinoma of the lung.
 JRC:6253 : cutaneous metastasis of a pulmonary oat cell carcinoma.
 JRC:6257 : Small cell carcinoma of the lung.
 JRC:6259 : Small cell carcinoma of the lung (Oat cell carcinoma of the lung).

Definition: Small cell undifferentiated carcinoma is the most aggressive of lung malignancies and is rated as grade 3 under the current WHO classification of neuroendocrine carcinomas. It accounts for 25% of all lung carcinomas.

It predominantly affects male tobacco users, usually starting in their fifties, and it commonly presents as a pulmonary mass of 1 to 5 cm in diameter. It is mainly located in the peri-hilar region and is usually metastasized by the time of diagnosis.

Macroscopy

Dun-grayish nodular formation with poorly-defined borders, fleshy appearance, small hemorrhagic areas and necrosis; it may be cavitated.

Microscopy

Composed of uniformly small cells (10-15 microns) which may be arranged in solid patterns, nests, trabeculae, or pseudo rosettes.

According to the current WHO classification (1999), the small cell lung carcinoma is divided into two types:
 1- "pure" small cell carcinoma

• a. oat cell sub-type
• b. intermediate cell sub-type

 2. combined small cell carcinoma.

Cytology

Small cells ranging from 1.5 to 2 times the size of a lymphocyte will be observed; nuclei are round or oval, centrally located with uniform chromatin, high nucleus-cytoplasm ratio and inconspicuous nucleoli.

It typically presents in clusters of tumor cells with marked molding and overlapping nuclear outlines.

In cytology samples, necrosis is evidenced by marked karyo-pyknosis, cytoplasm disintegration and formation of cyanophilous masses of necrotic debris.

In the intermediate cell sub-type of small cell undifferentiated carcinomas, nuclei are slightly larger, the cytoplasmic border is more marked, and they may contain a conspicuous nucleolus.

Morphological possibilities are diverse in the combined type depending on the SCC being associated with a squamous cell carcinoma, adenocarcinoma or large cell undifferentiated carcinoma.

The typical oat cell carcinoma is characterized for having cells which are approximately twice the size of a lymphocyte, with scanty cytoplasm, a high nucleus-cytoplasm ratio, nuclear hyperchromasia, finely granular chromatin and absent or inconspicuous nucleolus. Mitosis and necrosis are common elements of this tumor. Nuclei appear pyknotic and interspersed in areas of cell degeneration.

The intermediate cell variant of small cell carcinomas features cells with a chromatin arrangement similar to that of oat cells’, but with larger nuclei, evident nucleoli and more abundant cytoplasm.

The combined small cell carcinoma includes a small cell carcinoma component associated with a non-small cell carcinoma (squamous, large cells or adenocarcinoma).

All variants tend to show a lot of apoptosis, intense mitotic activity, scanty amphophilic cytoplasm and the so-called "Azzopardi phenomenon", which consists in an increase of basophilic nucleic acid adjacent to intratumoral blood vessels (seen by histology only).

Immunochemistry

 CD56+
 synaptophysin+
 chromogranin+
 TTF1+
 Ki67 80-90%

Electronic microscopy

Electronic microscopy allows verifying the existence of neurosecretion granules in most small cell undifferentiated carcinomas, and some of them have ultra-structural evidence of squamous or glandular differentiation; these last findings, however, do not modify the histological diagnosis.

Prognosis and treatment

At diagnosis, the disease is limited to the chest cavity in only a third of patients; the disease is spread in the remaining patients, with a remote possibility of long-term survival (less than 5%).

The American Joint Committee on Cancer (AJCC) staged this neoplasm in four grades, the first three of them (grades 1, 2 and 3) corresponding to the "limited" stage, and the last one (grade 4) to the "extended" stage from the old classification.

Although treatment is based on chemotherapy with or without radiotherapy, low-stage tumors are potentially resectable. Oat cell- (small cell) carcinomas and intermediate cell carcinomas have similar prognosis; it has been shown, however, that the combined type is more refractory to therapy.

Differential diagnosis

The first differential diagnosis is lymphoma, which differentiates from small cell carcinomas in the lack of intercellular cohesion and the absence of nuclear molding.

On the other hand, reserve cell hyperplasia is made up of small cells with hyperchromatic nucleus and scanty cytoplasm, and they may present molding. However, it differentiates from SCC because it has greater intercellular cohesion and cellular uniformity, in addition to smooth nuclear borders and an evident nucleolus.

It is necessary to distinguish SCC from non-small cell carcinomas, particularly from the poorly differentiated ones such as the poorly-differentiated squamous carcinoma, which have tumor cells with prominent nucleolus, a greater amount of cytoplasm, and dyskeratosis; chromatin, in turn, may cause a granulomatous reaction.

Poorly differentiated adenocarcinomas have eccentric nucleus, prominent nucleolus, and, possibly, mucin production.

The atypical carcinoid shares many of the characteristics of SCC, however its cells differ because they have evident nucleolus.

Links

 http://www.surgical-pathology.com/small_cell_carcinoma.htm
 http://www.sociedaddecitologia.org.ar/sac/index.php?option=com_content&view;=article&id;=141:carcinoma-indiferenciado-de-celulas-pequenas&catid;=7:fichas-tecnicas&Itemid;=6⟨=en

See also

 pulmonary carcinomas

• pulmonary tumors