Bone & Soft Tissue Pathology

Sarcomatoid/Spindle Cell Carcinoma of the Lung

Thomas V. Colby
Mayo Clinic
Scottsdale, AZ


Clinical History
(Case courtesy of Dr. G.H. Faber, Parkersburg, WV)

A 78 year old man with a 35 pack year smoking history was found to have a left apical mass on chest imaging studies. He came to lobectomy.


Slide 1
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Figure 1
Necrotic cellular mass with abnormal appearing small vessels in the adjacent lung tissue
Figure 2
Detail of the spindle cell proliferation comprising the mass
Figure 3
Detail of the spindle cell proliferation comprising the mass

Figure 4
Involvement of a relatively large pulmonary artery branch
Figure 5
High power of luminal proliferation seen in Figure 4
Figure 6
Small vessels in the lung tissue surrounding the mass

Figure 7
High power of the vessels shown in Figure 6
Figure 8
Small vessels in the lung tissue surrounding the mass
Figure 9
High power of the vessels shown in Figure 8


Diagnosis:
Sarcomatoid/spindle cell carcinoma of the lung.

Follow-up:
The patient died of his lung cancer one year later.

Key words:
Lung cancer, carcinoma of the lung, sarcomatoid carcinoma of the lung, sarcoma of the lung, spindle cell carcinoma of the lung, carcinosarcoma of the lung.

Key Points:
  • Sarcomatoid/spindle cell carcinomas of the lung may be mistaken for sarcomas or reactive processes

  • Many previously reported "sarcomas" of the lung (and probably all carcinosarcomas) were sarcomatoid carcinomas.

  • Synovial sarcoma is probably the most common sarcoma encountered in the lung in current practice (but these were not recognized until the 1990's).

  • Sarcomatoid carcinomas account for 1-5% of lung cancers.

  • Sarcomatoid carcinomas represent a subset of non-small cell lung cancers.

  • Sarcomatoid carcinomas have a worse prognosis than other non-small cell lung carcinomas.

  • The "sarcomatoid" regions of sarcomatoid carcinomas are thought to derive from the same clonal population of cells as the carcinomatous components (when carcinomatous areas are present) and this is thought to reflect epithelial mesenchymal transformation.

Sarcomatoid Carcinomas of the Lung
Sarcomatoid carcinomas mimic sarcomas because of the presence of spindle cells or matrix production/mesenchymal differentiation (or both). Depending on the patterns present terms such as spindle cell carcinoma and carcinosarcoma have been used. Differentiated mesenchymal elements encountered include rhabdomyosarcoma, osteosarcoma, chondrosarcoma, and rarely liposarcoma. With the development of immunohistochemical stains to recognize epithelial differentiation, the number of sarcomas reported in the lung has greatly decreased and, with the exception of synovial sarcoma, there have been few series of lung sarcomas since the 1980's. Nevertheless it is still said that one may encounter virtually any sarcoma in the lung, albeit rarely and in the 2008 review by Litzky the following were included: Leiomyosarcoma, Synovial sarcoma, Malignant peripheral nerve sheath tumor, Malignant solitary fibrous tumor, Epithelioid hemangioendothelioma, Angiosarcoma, Kaposi sarcoma, Inflammatory myofibroblastic tumor, Chondrosarcoma, Osteosarcoma, Liposarcoma, Fibrosarcoma, MFH, Hemangiopericytoma Pulmonary artery and vein sarcomas could be in this list as well. Surprisingly, synovial sarcoma, which is one of the most common, if not the most common sarcoma encountered in the lung, was not recognized until 1995. Cases with a large component of conventional carcinoma the diagnosis is relatively easy; cases in which carcinomatous elements are absent or inconspicuous present a diagnostic challenge.

Clues to spindle cell/sarcomatoid carcinoma include the following:
  • Sarcomatoid carcinomas are probably the most common malignancy encountered in the lung with a population of spindle cells (i.e. high pretest probably of sarcomatoid carcinoma)

  • Sarcomatoid carcinomas generally do not look like typical soft tissue sarcomas.

  • The nuclear features are more typical of carcinoma.

  • Sarcomatoid carcinomas have a marked propensity for vascular invasion.

  • Sarcomatoid carcinomas may show interstitial growth and surround alveolar spaces lined by reactive Type 2 cells.
Because of the various growth patterns individual cases may mimic an abscess or organizing pneumonia: so-called inflammatory sarcomatoid carcinoma. A myofibroblastic appearance to the tumor cells may mimic inflammatory myofibroblastic tumor. Some cases produce spaces resembling blood vascular spaces: so called pseudoangiosarcomatous sarcomatoid carcinoma. Immunohistochemistry is straightforward when there is a recognizable differentiated carcinomatous element present. Mesenchymal element show the typical staining pattern of that sort of differentiation. Problems with immunohistochemistry may be encountered when there is a pure spindle cell component. When this component is diffusely and strongly positive for epithelial markers the diagnosis is easy. Some cases show only spotty positivity and there may be large regions of the tumor (sometimes several blocks) that are negative for epithelial markers. When a sarcomatoid carcinoma is suspected one should try a number of epithelial markers such as AE1/AE3, CAM5.2, EMA, CEA and others. In some cases only one or two markers show appreciable positivity. Because epithelial differentiation may be only focal either on the histology or immunohistochemistry, sampling is important in these lesions. Epithelial differentiation may also be documented with electron microscopy but in most laboratories immunohistochemistry has replaced electron microscopy in routine practice.

Sarcomatoid Carcinomas in the WHO Classification
In the 2004 WHO classification of lung tumors the following were included under the category sarcomatoid carcinoma:
  • Pleomorphic carcinoma

  • Spindle cell carcinoma

  • Giant cell carcinoma

  • Carcinosarcoma

  • Pulmonary blastoma
By convention an individual component must involve at least 10% of a given tumor in order for the designation to apply. Sarcomatoid carcinomas composed entirely of spindle cells (spindle cell carcinoma) pose the greatest difficulty in separation from sarcoma. This spindle cell component in spindle cell carcinomas may show some positive staining with actin, desmin, and S-100.

Clinical Aspects of Sarcomatoid Carcinomas of the Lung
Sarcomatoid carcinomas account for 1-5% of all lung cancers. 90% of the patients are smokers and the median age is ~ 60 years. Men are affected more often than women (with ratios varying from slightly greater than 1:1 to 10:1 in various series). While one or two series suggested that the prognosis was similar to that of other small cell lung cancers, stage for stage, most recent series suggest that this form of lung cancer is a particularly aggressive and the prognosis is worse stage for stage than other non-small cell lung cancer. Sarcomatoid carcinomas represent variants of non-small cell lung cancer and should be managed as such. As with lung cancer in general it is important in such cases to identify whether there is any squamous or glandular differentiation (TTF-1, CK 5/6, p63 staining); in individual cases other studies, including molecular studies (EGFR, K-ras, RRM1, ERCC1, BRCA) may be requested to guide therapy.

Sarcomatoid Carcinomas of the Lung - Histogenesis
As in other organ systems that show tumors with divergent histology, it is currently accepted that sarcomatoid carcinomas in the lung, including those with both carcinomatous and sarcomatous elements, represent malignancies of a single clone showing divergent differentiation. Methods to confirm have included allelotyping, K-ras mutational genotyping, and comparative genomic hybridization. Indeed one can often encounter histologic, immunoistochemical, and electron microscopic transitions between cells showing epithelial features and those showing mesenchymal features. These tumors are thought to reflect an epithelial mesenchymal transformation.

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