Carcinoma ex Pleomorphic Adenoma: A Comprehensive Review of Clinical, Pathological and Molecular Data

Abstract

Carcinoma ex pleomorphic adenoma (Ca ex PA) is a carcinoma arising from a primary or recurrent benign pleomorphic adenoma. It often poses a diagnostic challenge to clinicians and pathologists. This study intends to review the literature and highlight the current clinical and molecular perspectives about this entity. The most common clinical presentation of CA ex PA is of a firm mass in the parotid gland. The proportion of adenoma and carcinoma components determines the macroscopic features of this neoplasm. The entity is difficult to diagnose pre-operatively. Pathologic assessment is the gold standard for making the diagnosis. Treatment for Ca ex PA often involves an ablative surgical procedure which may be followed by radiotherapy. Overall, patients with Ca ex PA have a poor prognosis. Accurate diagnosis and aggressive surgical management of patients presenting with Ca ex PA can increase their survival rates. Molecular studies have revealed that the development of Ca ex PA follows a multistep model of carcinogenesis, with the progressive loss of heterozygosity at chromosomal arms 8q, then 12q and finally 17p. There are specific candidate genes in these regions that are associated with particular stages in the progression of Ca ex PA. In addition, many genes which regulate tumour suppression, cell cycle control, growth factors and cell-cell adhesion play a role in the development and progression of Ca ex PA. It is hopeful that these molecular data can give clues for the diagnosis and management of the disease.

Current Thinking on Malignant Salivary Gland Neoplasms

“…CXPA predominantly affects the major salivary glands with a majority of cases noted in the parotid and submandibular glands. The cancer has been known to manifest in the minor salivary glands in the oral cavity, particularly the hard and soft palate [54][55][56]. It has a prevalence rate of 5.6 cases per 100,000 malignant neoplasm's and a yearly incidence rate of 0.17 tumors per one million persons [51].…”

“…It has a prevalence rate of 5.6 cases per 100,000 malignant neoplasm's and a yearly incidence rate of 0.17 tumors per one million persons [51]. This malignancy is found predominantly in the sixth to eighth decades of life and is slightly more common in females [56].…”

Invasive salivary duct carcinoma ex pleomorphic adenoma of the parotid gland: a teaching case giving rise to the genuine diagnostic difficulty on an inadequate cytology specimen

“…Despite of that, Ca ex PA is uncommon and has a prevalence rate of 5.6 cases per 100,000 malignant neoplasms and a yearly incidence rate of 0.17 tumors per 1 million people [1,2]. This neoplasm is defined as an epithelial malignant transformation within a primary (de novo) or recurrent PA, and often poses a diagnostic challenge to clinicians and cytopathologists, since its entity is difficult to diagnose pre-operatively [3,4].…”

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

“…For example, in a recent series on 41 cases of Ca ex PA, only 2 cases (5 %) were labeled as CS [5], in a series comprising 73 cases, 1 case (1.4 %) was diagnosed as sarcomatoid carcinoma [6] and in the series by Katabi et al [7] of 43 cases of Ca ex Pa, 1 case (2.3 %) was a CS. Surprisingly, in a recent review on Ca ex PA, the occurrence of CS in this setting was not mentioned at all [8]. The series on malignant transformation of PA with the highest frequency of CS and sarcomatoid carcinoma was from Japan [9].…”

“…The role of TP53 in malignant transformation of PA is complex and has been nicely summarized in a recent paper in this journal [8]. A few points of interest are: (1) Frequent loss of 17p (where TP53 is located) has been reported [34] and (2) both overexpression of p53 and TP53 mutations have been reported [27,39].…”