Sarcomatoid carcinoma of the lung pathophysiology

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Trusha Tank, M.D.[2]

Overview

Sarcomatoid carcinomas are rare, aggressive, malignant cancer and can occur in different organs such as the thyroid gland, bone, skin, breast, pancreas, liver, urinary tract, and lung. Sarcomatoid carcinoma of the lung is a group of poorly differentiated non-small cell lung carcinomas. Sarcomatoid carcinoma is defined as a biphasic tumor with morphological characteristics of both, carcinomatous and sarcomatous components. The exact pathogenesis of sarcomatoid carcinoma of the lung is not fully understood, but the EGFR and K-ras gene mutations have been associated with the development of sarcomatoid carcinoma of the lung.

Pathophysiology

Physiology

The normal physiology of [name of process] can be understood as follows:

Pathogenesis

• The pathogenesis of sarcomatoid carcinoma of the lung is characterized by a rare epithelial origin and morphologic features suggestive of a malignant mesenchymal tumor.
• Four major hypotheses may explain sarcomatoid neoplasms:
  • The embryonic rest hypothesis: This theory suggests that sarcomatoid tumors are the result of misplaced “mini-organs” that has epithelial and stromal component.
  • The collision hypothesis: This theory implies separate but concomitant malignant proliferation of epithelium and mesenchyme.
  • The stromal induction/metaplasia hypothesis: This theory suggests that sarcomatous elements are an atypical response to the growth of a carcinoma.
  • Totipotential hypothesis: This hypothesis proposes an origin from a single totipotential stem cell that differentiates into epithelial and mesenchymal components.

Genetics

• The development of sarcomatoid carcinoma is the result of multiple genetic mutations such as:
• EGFR
• K-ras

Associated Conditions

There are no conditions associated with sarcomatoid carcinoma of the lung.

Gross Pathology

• Sarcomatoid carcinomas can arise centrally or peripherally.
• Most commonly present as poorly circumscribed solitary peripheral masses.
• Sarcomatoid carcinoma is commonly found in upper lobe of lungs.
• Tumors are large, ranging from 1 to 13 cm, with a median of 4.9 cm, and often invade the chest wall.
• Tumor consistency is described as soft and fleshy or firm, hard, or rubbery.
• Cut surfaces vary from white-grey to yellow, frequently show hemorrhagic and necrotic foci, and occasionally demonstrate cavitation.

Microscopic Pathology

• On microscopic histopathologically sarcomatoid carcinoma is classified into 5 subtypes:
  • Pleomorphic carcinoma
    • Poorly differentiated, sarcomatoid carcinoma composed of malignant, spindle and giant cells.
    • Spindle cell may vary from epithelioid to strikingly spindled and are arranged in haphazard fascicles or storiform pattern.
    • Giant cells are discohesive, uni/multinucleated, have moderate to abundant, dense, eosinophilic cytoplasm which may show emperipolesis by polymorphonuclear leukocytes or lymphocytes.
    • Giant cells are anaplastic, with many bizarre forms.
    • Tumor cells are embedded in a fibrous or myxoid stroma.
  • Spindle cell carcinoma
    • Sarcomatoid carcinoma composed only of spindle-shaped tumor cells.
  • Giant cell carcinoma
    • Sarcomatoid carcinoma composed only of anaplastic, giant tumor cells.
  • Carcinosarcoma
    • A mixture of carcinoma and true sarcomas such as osteosarcoma, chondrosarcoma or rhabdomyosarcoma.
    • The carcinoma component may be squamous cell carcinoma, adenocarcinoma, adenocarcinoma mixed with squamous cell carcinoma, and large cell carcinoma, whereas the sarcoma component may be rhabdomyosarcoma, osteosarcoma mixed with chondrosarcoma, and osteosarcoma.
  • Pulmonary blastoma
    • A biphasic tumor composed of a primitive epithelial component with well-differentiated, fetal adenocarcinoma and a primitive mesenchymal stroma that may contain rhabdomyosarcoma, osteosarcoma, or chondrosarcoma.