Pan‐TRK immunohistochemistry in gynaecological mesenchymal tumours: diagnostic implications and pitfalls

Aims NTRK‐rearranged sarcomas of the female genital tract mainly occur in the uterus (more commonly cervix than corpus) and are characterized by a “fibrosarcoma‐like” morphology and NTRK gene rearrangements. These neoplasms may exhibit histological overlap with other entities and can present diagnos...

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Veröffentlicht in:Histopathology Jg. 84; H. 3; S. 451 - 462
Hauptverfasser: Moura, Madalena Souto, Costa, João, Velasco, Valérie, Kommoss, Felix, Oliva, Esther, Le Loarer, Francois, McCluggage, W Glenn, Razack, Rubina, Treilleux, Isabelle, Mills, Anne, Longacre, Teri, Devouassoux‐Shisheboran, Mojgan, Hostein, Isabelle, Azmani, Rihab, Blanchard, Larry, Hartog, Cécile, Soubeyran, Isabelle, Khalifa, Emmanuel, Croce, Sabrina
Format: Journal Article
Sprache:Englisch
Veröffentlicht: England Wiley Subscription Services, Inc 01.02.2024
Schlagworte:
CD34 antigen
Cervix
DNA microarrays
Endometrium
Fibrosarcoma
Fluorescence in situ hybridization
Genital tract
Gynecology
Immunohistochemistry
NTRK
pan‐TRK
Sarcoma
Smooth muscle
Tumors
uterine neoplasm
Uterus
sarcoma
NTRK
immunohistochemistry
uterine neoplasm
fibrosarcoma
pan-TRK
ISSN:0309-0167, 1365-2559, 1365-2559
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Zusammenfassung:Aims NTRK‐rearranged sarcomas of the female genital tract mainly occur in the uterus (more commonly cervix than corpus) and are characterized by a “fibrosarcoma‐like” morphology and NTRK gene rearrangements. These neoplasms may exhibit histological overlap with other entities and can present diagnostic difficulties without molecular confirmation. Pan‐TRK immunohistochemistry was developed to identify tumours harbouring NTRK rearrangements. The aim of this study was to characterize pan‐TRK immunohistochemical expression in a large cohort of gynaecological mesenchymal neoplasms and investigate the utility of pan‐TRK immunohistochemistry to distinguish NTRK‐rearranged sarcoma from its mimics. Methods and results A total of 473 gynaecological mesenchymal tumours (461 without known NTRK fusions and 12 NTRK‐rearranged sarcomas) were selected. Pan‐TRK immunohistochemistry (EPR17341, Abcam) was performed on whole tissue sections and tissue microarrays. Molecular interrogation of pan‐TRK positive tumours was performed by RNA sequencing or fluorescence in situ hybridization (FISH). Of the 12 NTRK‐rearranged sarcomas, 11 (92%) exhibited diffuse (≥70%) cytoplasmic pan‐TRK staining with moderate/marked intensity, while the other was negative. Eleven (2.4%) additional tumours also exhibited pan‐TRK immunohistochemical expression: three low‐grade endometrial stromal sarcomas, seven high‐grade endometrial stromal sarcomas, and an undifferentiated uterine sarcoma. Molecular confirmation of the absence of NTRK rearrangements was possible in nine of these tumours. Of these nine neoplasms, seven exhibited focal/multifocal (<70%) pan‐TRK cytoplasmic staining with weak/moderate intensity. Conclusion Even though pan‐TRK immunohistochemical expression is not entirely sensitive or specific for NTRK‐rearranged sarcomas, these neoplasms tend to exhibit diffuse staining of moderate/strong intensity, unlike its mimics. Pan‐TRK should be performed in monomorphic uterine (corpus and cervix) spindle cell neoplasms that are negative for smooth muscle markers and hormone receptors and positive for CD34 and/ or S100. Ultimately, the diagnosis requires molecular confirmation. Uterine mesenchymal neoplasms with a fibrosarcoma‐like morphology should be tested by pan‐TRK immunohistochemistry. Tumours with diffuse staining for pan‐TRK with moderate/marked intensity have a high likelihood of harbouring NTRK rearrangements. Tumours with focal/multifocal staining for pan‐TRK with weak/moderate intensity or negative have a low likelihood of harbouring NTRK rearrangements.
Bibliographie:Madalena Souto Moura and João Costa equally contributed to the article and are both co‐first authors.
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ISSN:0309-0167
1365-2559
1365-2559
DOI:10.1111/his.15082