PMID- 31094927
OWN - NLM
STAT- MEDLINE
DCOM- 20200323
LR  - 20200323
IS  - 1532-0979 (Electronic)
IS  - 0147-5185 (Linking)
VI  - 43
IP  - 8
DP  - 2019 Aug
TI  - Metastasizing Pleomorphic Adenoma: Recurrent PLAG1/HMGA2 Rearrangements and 
      Identification of a Novel HMGA2-TMTC2 Fusion.
PG  - 1145-1151
LID - 10.1097/PAS.0000000000001280 [doi]
AB  - Pleomorphic adenoma (PA) is the most common salivary gland neoplasm. On a 
      molecular level PA is characterized by a translocation involving PLAG1 or HMGA2. 
      PA is considered to be a benign tumor although it can undergo malignant 
      transformation. Alternatively, cases of histologically benign PA "metastasizing" 
      to lymph nodes or distant body sites are well documented. Several theories have 
      been proposed to explain this behavior. However, there is a lack of molecular 
      data available to assess the relationship of metastasizing PA (MPA) and their 
      benign counterparts. In this study we describe 4 cases of MPAs and perform the 
      first molecular study linking them to conventional PA. The index case was 
      identified in the course of routine clinical practice, while the other cases were 
      retrieved from the archives of the authors. Slides were reviewed to confirm the 
      diagnosis of both the primary/recurrent tumor and the metastasis. Fluorescence in 
      situ hybridization (FISH) was performed in all cases and RNA sequencing was 
      performed on the index case. In all cases there was a history of recurrent PA 
      involving the parotid. Lymph node metastases were identified in 2 cases; 
      non-lymph node metastases were identified in 3 cases. All the metastases were 
      histologically benign. RNA sequencing performed on the index case demonstrated a 
      novel HMGA2-TMTC2 translocation, which was confirmed by separate FISH break-apart 
      assays for both genes. FISH performed on the remaining cases demonstrated 
      rearrangement of PLAG1 in all 3 cases. This study demonstrates that MPA harbors 
      the same disease-defining molecular hallmark as their benign counterparts.
FAU - Wasserman, Jason K
AU  - Wasserman JK
AD  - Department of Pathology and Laboratory Medicine, Division of Anatomical 
      Pathology, The Ottawa Hospital/University of Ottawa.
FAU - Dickson, Brendan C
AU  - Dickson BC
AD  - Department of Pathology and Laboratory Medicine, Mount Sinai Hospital.
AD  - Department of Laboratory Medicine and Pathobiology, University of Toronto.
FAU - Smith, Adam
AU  - Smith A
AD  - Department of Laboratory Medicine and Pathobiology, University of Toronto.
AD  - Laboratory Medicine Program, University Health Network.
FAU - Swanson, David
AU  - Swanson D
AD  - Department of Pathology and Laboratory Medicine, Mount Sinai Hospital.
AD  - Department of Laboratory Medicine and Pathobiology, University of Toronto.
FAU - Purgina, Bibianna M
AU  - Purgina BM
AD  - Department of Pathology and Laboratory Medicine, Division of Anatomical 
      Pathology, The Ottawa Hospital/University of Ottawa.
FAU - Weinreb, Ilan
AU  - Weinreb I
AD  - Department of Laboratory Medicine and Pathobiology, University of Toronto.
AD  - Department of Pathology, University Health Network, Toronto, ON, Canada.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Am J Surg Pathol
JT  - The American journal of surgical pathology
JID - 7707904
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (Carrier Proteins)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (HMGA2 Protein)
RN  - 0 (HMGA2 protein, human)
RN  - 0 (Membrane Proteins)
RN  - 0 (PLAG1 protein, human)
RN  - 0 (TMTC2 protein, human)
SB  - IM
MH  - Adenoma, Pleomorphic/chemistry/*genetics/*pathology/surgery
MH  - Adult
MH  - Biomarkers, Tumor/analysis/*genetics
MH  - Carrier Proteins/*genetics
MH  - DNA-Binding Proteins/*genetics
MH  - Female
MH  - *Gene Fusion
MH  - *Gene Rearrangement
MH  - Genetic Predisposition to Disease
MH  - HMGA2 Protein/*genetics
MH  - Humans
MH  - Immunohistochemistry
MH  - In Situ Hybridization, Fluorescence
MH  - Lymphatic Metastasis
MH  - Male
MH  - Membrane Proteins/*genetics
MH  - Neoplasm Recurrence, Local
MH  - Phenotype
MH  - Salivary Gland Neoplasms/chemistry/*genetics/*pathology/surgery
MH  - Treatment Outcome
EDAT- 2019/05/17 06:00
MHDA- 2020/03/24 06:00
CRDT- 2019/05/17 06:00
PHST- 2019/05/17 06:00 [pubmed]
PHST- 2020/03/24 06:00 [medline]
PHST- 2019/05/17 06:00 [entrez]
AID - 10.1097/PAS.0000000000001280 [doi]
PST - ppublish
SO  - Am J Surg Pathol. 2019 Aug;43(8):1145-1151. doi: 10.1097/PAS.0000000000001280.