Disseminated Carcinoma Ex Pleomorphic Adenoma in an Adolescent Confirmed by Application of PLAG1 Immunohistochemistry and FISH for PLAG1 Rearrangement

Abstract

A 16-year-old previously asymptomatic boy presented with complaints of fatigue, weight loss, and back pain for several months. Imaging studies revealed a large superior mediastinal mass, numerous bilateral pulmonary nodules, and multiple lytic bone lesions. A needle biopsy from a sternal lesion showed a poorly differentiated carcinoma, immunoreactive for cytokeratins and EMA and immunonegative for various organ/tissue-specific markers. His past medical history was significant for excision of a parotid gland tumor 5 years earlier. Histologic review of the salivary gland tumor revealed a pleomorphic adenoma containing a microscopic focus of invasive carcinoma (carcinoma ex pleomorphic adenoma). By immunohistochemistry, both the salivary gland tumor and the disseminated carcinoma expressed PLAG1 with a strong nuclear pattern. Fluorescence in situ hybridization (FISH), using dual-color, break-apart probes for PLAG1, showed rearrangement of the gene in both the salivary gland and the disseminated tumors. FISH demonstrated additional cytogenetic aberrations in the carcinoma, including polysomy for chromosome 8 (in both the primary salivary gland and the metastatic tumors) and PLAG1 amplification (in the metastatic tumor). We conclude that in the proper clinicopathologic setting, application of PLAG1 immunohistochemistry and FISH for PLAG1 gene rearrangement may be valuable in establishing the diagnosis of carcinoma ex pleomorphic adenoma as the source of a cancer of unknown primary site.

PLAG1 Alteration in Carcinoma Ex Pleomorphic Adenoma: Immunohistochemical and Fluorescence In Situ Hybridization Studies of 22 Cases

“…Tsang et al [16] reported a case of CA-ex-PA with amplification of multiple genes including PLAG1 [16]. We have also recently demonstrated increased copy number and amplification of rearranged PLAG1 in a CA-ex-PA in a young patient who had a history of PA with simple PLAG1 rearrangement [38]. An additional case in our current series showed amplification of altered PLAG1.…”

An analysis of PLAG1 and HMGA2 rearrangements in salivary duct carcinoma and examination of the role of precursor lesions

“…Interphase fluorescence in‐situ hybridization (FISH) studies were performed on 4‐μm‐thick sections of the TMA, with a custom dual‐colour, break‐apart probe for PLAG1 , and a dual‐colour, break‐apart probe for HMGA2 , as previously described . In addition, a FISH assay was designed to determine the copy number status of PLAG1 , with bacterial artificial clone RP11‐140I16, in relation to the number of copies of the chromosome 8 centromere probe.…”

Clinicopathological effect of PLAG1 fusion genes in pleomorphic adenoma and carcinoma ex pleomorphic adenoma with special emphasis on histological features

“…The most common histological subtype of CXPA is salivary duct carcinoma (SDC), followed by myoepithelial carcinoma (MYC) and adenocarcinoma not otherwise specified (NOS), although CXPA can present any histological subtype of salivary gland malignant tumour . Similar to PA, PLAG1 / HMGA2 rearrangements are the most frequently observed genetic events in CXPA, and detection of PLAG1 expression or PLAG1 rearrangements are practically used to distinguish PA and CXPA from other benign or malignant salivary tumours . PLAG1 is presumed to play an important role in CXPA; however, it is poorly understood, especially in the context of CXPA morphology …”

“…1,19 Similar to PA, PLAG1/HMGA2 rearrangements are the most frequently observed genetic events in CXPA, 20 and detection of PLAG1 expression or PLAG1 rearrangements are practically used to distinguish PA and CXPA from other benign or malignant salivary tumours. 20,21 PLAG1 is presumed to play an important role in CXPA; however, it is poorly understood, especially in the context of CXPA morphology. [22][23][24] In this study, we analysed PLAG1 and HMGA2 gene fusions in PAs by reverse transcription-polymerase chain reaction (RT-PCR) and examined the relationship between the fusion genes and the clinicopathological characteristics of PAs.…”