PMID- 34506648
OWN - NLM
STAT- MEDLINE
DCOM- 20220331
LR  - 20220331
IS  - 1365-2559 (Electronic)
IS  - 0309-0167 (Linking)
VI  - 80
IP  - 2
DP  - 2022 Jan
TI  - Primary mediastinal germ cell tumours: an immunohistochemical and molecular 
      diagnostic approach.
PG  - 381-396
LID - 10.1111/his.14560 [doi]
AB  - AIMS: Primary mediastinal germ cell tumours (PMGCTs) are rare mediastinal 
      neoplasms, and their diagnosis can be challenging, owing to small biopsy samples. 
      The aim of this study was to develop a diagnostic algorithm using 
      immunohistochemical staining, with a focus on novel markers, and molecular 
      analysis of isochromosome 12p [i(12p)]. METHODS AND RESULTS: Paraffin-embedded 
      tissues of 32 mediastinal tumours were analysed with immunohistochemical staining 
      for sal-like transcription factor 4 (SALL4), Lin-28 homologue A (LIN28), 
      octamer-binding transcription factor 3/4 (OCT3/4), D2-40, cluster of 
      differentiation 117 (CD117), sex-determining region Y-box 17, sex-determining 
      region Y-box 2 (SOX2), cluster of differentiation 30, the beta-subunit of human 
      chorionic gonadotropin (beta-hCG), GATA-binding protein 3 (GATA3), forkhead box 
      protein A2 (FOXA2), glypican-3 (GPC3), alpha-fetoprotein (AFP), terminal 
      deoxynucleotidyl transferase (TdT), nuclear protein of the testis (NUT), and 
      pan-cytokeratin. Quantitative real-time polymerase chain reaction was performed 
      to investigate the i(12p) status. Fifteen seminomas, seven teratomas, one yolk 
      sac tumour, one choriocarcinoma and seven mixed PMGCTs were diagnosed. Each 
      entity had different immunohistochemical staining patterns, which helped to 
      distinguish them: OCT3/4, D2-40, CD117 and TdT for seminoma; OCT3/4 and SOX2 for 
      embryonal carcinoma; FOXA2, GPC3 and AFP for yolk sac tumour; and beta-hCG and GATA3 
      for choriocarcinoma. Mature teratomas stained positively for pan-cytokeratin in 
      epithelial components and focally for SALL4, SOX2, GATA3, D2-40, and FOXA2. 
      Furthermore, a NUT carcinoma mimicking a PMGCT was diagnosed, showing strong 
      nuclear SOX2 staining and speckled nuclear NUT staining. i(12p) was detected in 
      24 of 27 PMGCTs (89%). CONCLUSION: A diagnostic algorithm is of great importance 
      for a reliable diagnosis of PMGCT in, usually small, tissue biopsy samples. 
      Therefore, a combination of three to four antibodies to identify the correct 
      histological subtype is usually necessary, in addition to morphological features. 
      The i(12p) status serves as an additional option to indicate a germ cell origin 
      in selected cases.
CI  - (c) 2021 The Authors. Histopathology published by John Wiley & Sons Ltd.
FAU - Fichtner, Alexander
AU  - Fichtner A
AUID- ORCID: 0000-0003-3942-2289
AD  - Institute of Pathology, University Medical Centre Gottingen, Gottingen, Germany.
FAU - Richter, Annika
AU  - Richter A
AD  - Institute of Pathology, University Medical Centre Gottingen, Gottingen, Germany.
FAU - Filmar, Simon
AU  - Filmar S
AD  - Institute of Pathology, University Medical Centre Gottingen, Gottingen, Germany.
FAU - Kircher, Stefan
AU  - Kircher S
AD  - Institute of Pathology, University of Wurzburg, Wurzburg, Germany.
FAU - Rosenwald, Andreas
AU  - Rosenwald A
AD  - Institute of Pathology, University of Wurzburg, Wurzburg, Germany.
FAU - Kuffer, Stefan
AU  - Kuffer S
AUID- ORCID: 0000-0001-8443-601X
AD  - Institute of Pathology, University Medical Centre Gottingen, Gottingen, Germany.
FAU - Nettersheim, Daniel
AU  - Nettersheim D
AD  - Department of Urology, Urological Research Laboratory, Translational UroOncology, 
      Medical Faculty and University Hospital Dusseldorf, Heinrich-Heine-University, 
      Dusseldorf, Germany.
FAU - Oing, Christoph
AU  - Oing C
AD  - Division of Pneumology, Department of Oncology, Haematology and Bone Marrow 
      Transplantation, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
AD  - Mildred Scheel Cancer Career Centre HaTriCS4, Hamburg, Germany.
FAU - Marx, Alexander
AU  - Marx A
AD  - Institute of Pathology, University Medical Centre Mannheim, Mannheim, Germany.
FAU - Strobel, Philipp
AU  - Strobel P
AD  - Institute of Pathology, University Medical Centre Gottingen, Gottingen, Germany.
FAU - Bremmer, Felix
AU  - Bremmer F
AUID- ORCID: 0000-0003-0367-6527
AD  - Institute of Pathology, University Medical Centre Gottingen, Gottingen, Germany.
LA  - eng
GR  - 2016.041.1/Wilhelm Sander-Stiftung/
GR  - 2016.041.2/Wilhelm Sander-Stiftung/
GR  - 2016.041.3/Wilhelm Sander-Stiftung/
PT  - Journal Article
DEP - 20211116
PL  - England
TA  - Histopathology
JT  - Histopathology
JID - 7704136
RN  - 0 (Biomarkers, Tumor)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Algorithms
MH  - Biomarkers, Tumor/metabolism
MH  - Child
MH  - Female
MH  - Humans
MH  - Immunohistochemistry
MH  - Male
MH  - Mediastinal Neoplasms/*diagnosis/metabolism/pathology
MH  - Middle Aged
MH  - Neoplasms, Germ Cell and Embryonal/*diagnosis/metabolism/pathology
MH  - Pathology, Molecular
MH  - Young Adult
OTO - NOTNLM
OT  - NUT carcinoma
OT  - germ cell tumour
OT  - immunohistochemistry
OT  - isochromosome 12p
OT  - mediastinum
OT  - qPCR
EDAT- 2021/09/11 06:00
MHDA- 2022/04/01 06:00
CRDT- 2021/09/10 17:26
PHST- 2021/08/24 00:00 [revised]
PHST- 2021/05/08 00:00 [received]
PHST- 2021/09/06 00:00 [accepted]
PHST- 2021/09/11 06:00 [pubmed]
PHST- 2022/04/01 06:00 [medline]
PHST- 2021/09/10 17:26 [entrez]
AID - 10.1111/his.14560 [doi]
PST - ppublish
SO  - Histopathology. 2022 Jan;80(2):381-396. doi: 10.1111/his.14560. Epub 2021 Nov 16.