Carcinosarcoma ex Non-Recurrent Pleomorphic Adenoma Composed of TTF-1 Positive Large Cell Neuroendocrine Carcinoma and Myofibrosarcoma: Apropos a Rare Case

Abstract

We present a carcinosarcoma ex non-recurrent pleomorphic adenoma composed of a large cell neuroendocrine carcinomatous component and a spindle cell sarcoma with myofibroblastic differentiation. The tumor contained a hyalinized transition zone where the classical PA appeared to acquire two different histopathological patterns of malignant transformation of the epithelial component. The carcinomatous component was strongly and diffusely positive for low-molecular weight cytokeratins (AE1-3), synaptophysin, thyroid transcription factor-1 and focally positive for chromogranin A. All these markers were negative in the sarcomatous component. The sarcomatous component displayed immunoreactivity for smooth muscle actin with a predominantly linear, subplasmalemmal pattern. No expression of CD31, S100 protein, h-caldesmon, desmin, CD34, p63, myogenin, Myo D1 and c-kit was detected. Strong immunohistochemical expression of p53 was documented in both the carcinomatous and sarcomatous components as well as in the atypical epithelial component in the transition zone associated with the hyalinized pleomorphic adenoma.

Salivary carcinosarcoma: insight into multistep pathogenesis indicates uniform origin as sarcomatoid variant of carcinoma ex pleomorphic adenoma with frequent heterologous elements

“…Intracapsular malignant tumour within PA was present in 12 patients (no. [1][2][3][4][5][6][7][8][9][10][11][12]. Intraductal carcinoma was present in 9/12 (no.…”

“…The prevailing terminology until 1990 was (true) malignant mixed tumour, 1,2,6,7,9,10 while carcinosarcoma was regularly used thereafter. [3][4][5]8,[11][12][13][14] Cases of SCS ex PA represented 3%-6% in large CEPA series. 2,20 The average age was 60.1 years (10-86), 57.3% were male, 70.3% in parotid, 18.9% in submandibular, and 11.8% in minor glands.…”

“…Analogous to the historic term "benign mixed tumour" (now pleomorphic adenoma, PA), this tumour type was initially called "true malignant mixed tumour", with, at that time, a blurred distinction from carcinoma ex pleomorphic adenoma (CEPA). 1,2,[6][7][8][9][10] Later, SCS became the universally accepted terminology [3][4][5]8,[11][12][13][14] and remained so in the current 4th 11 and upcoming 5th 15 WHO classification of salivary tumours. The distinction of SCS from high-grade sarcomatoid dedifferentiation of primary salivary carcinoma (mostly salivary duct carcinoma, SDC) has not been clearly defined.…”

“…An associated PA has been described in half of the cases. 1,[3][4][5][8][9][10][11][12] However, this figure may be too low, as the frequency of PA detection is strongly influenced by awareness of this association, the extent of tissue sampling, and the fact that sclerosed PA can be misinterpreted as regressive changes. In addition, the relationship between carcinomatous and sarcomatous components has been disputed (as in carcinosarcoma of other organs 18 ).…”

“…A clonal relationship between both components has been proven, 14,18 and derivation of the sarcomatous component has been postulated from myoepithelial cells of PA and from primary carcinomatous components. 1,4,[8][9][10]12 Concerning CEPA, a complex multistep carcinogenesis has been characterised. With the exception of the myoepithelial type, intracapsular CEPA generally starts as intraductal neoplasia within the biphasic tubules of PA.…”