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Paratesticular desmoplastic small round cell tumour: an unusual tumour with an unusual fusion; cytogenetic and molecular genetic analysis combining RT-PCR and COBRA-FISH.

Cliteur VP, Szuhai K, Baelde HJ, van Dam J, Gelderblom H, Hogendoorn PC - Clin Sarcoma Res (2012)

Bottom Line: The EWSR1-WT1 chimera seems to function as an oncogenic transcription factor.Here the zinc finger domain of the WT1 acts with affinity with certain promoter domains influencing the expression of various downstream proteins such as: PDGFA, PAX2, insulin-like growth factor 1 receptor, epidermal growth factor receptor, IL2 receptor beta, BAIAP3, MLF1, TALLA-1, LRRC15 and ENT.We discuss their potential oncogenic roles and potential therapeutic consequences.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pathology, Leiden University Medical Center, Leiden, Albinusdreef 2, Leiden, The Netherlands. P.C.W.Hogendoorn@lumc.nl.

ABSTRACT
Desmoplastic small round cell tumour is a rare malignant tumour with a male to female ratio of 4:1. It manifests mostly at serosal sites. Here we present a case of a 28-year-old male patient, who presented with a fast growing paratesticular mass. On biopsy nests and cords of small round cells, without a clear morphological lineage of differentiation were seen. Occasionally desmoplatic small round cell tumour shows different lines of differentiation. An unequivocal histological diagnosis might be difficult in such cases. Here we demonstrate by a combination of methods the characteristic immunohistochemical profile and - albeit unusual - molecular background and discuss the eventual link with Ewing sarcoma.Immunohistochemical studies showed a membranous staining of Keratine AE1/3 and a dot-like staining of Desmine, confirming its diagnosis. Using COBRA-FISH following a metaphase approach we demonstrated a balanced translocation, t(11;22)(p13;q12) and in RT-PCR formation of the EWSR1-WT1 fusion product, a specific translocation of desmoplastic round cell tumour. The fusion involves exon 9 of EWSR1 to exon 8 of WT1, an unusual fusion product, though earlier described in a case of a desmoplastic small round cell tumour of the hand. The EWSR1-WT1 chimera seems to function as an oncogenic transcription factor. Here the zinc finger domain of the WT1 acts with affinity with certain promoter domains influencing the expression of various downstream proteins such as: PDGFA, PAX2, insulin-like growth factor 1 receptor, epidermal growth factor receptor, IL2 receptor beta, BAIAP3, MLF1, TALLA-1, LRRC15 and ENT. We discuss their potential oncogenic roles and potential therapeutic consequences.

No MeSH data available.


Related in: MedlinePlus

Macro- and microscopic features. A: gross specimen. The tumour masses were solid, firm, with grey-white cut surfaces and areas of necrosis. B: light micrograph showing compact nests and sheets of small, round cells in desmoplastic stroma. Magnification 25× C: numerous mitotic figures can be observed. Magnification 200× D: Immunohistochemical detection of desmin; the reaction shows a typical paranuclear dot-like staining. Magnification 200×.
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Figure 1: Macro- and microscopic features. A: gross specimen. The tumour masses were solid, firm, with grey-white cut surfaces and areas of necrosis. B: light micrograph showing compact nests and sheets of small, round cells in desmoplastic stroma. Magnification 25× C: numerous mitotic figures can be observed. Magnification 200× D: Immunohistochemical detection of desmin; the reaction shows a typical paranuclear dot-like staining. Magnification 200×.

Mentions: Sections obtained from the testicular tumour mass (Figure 1A) were composed of sharply defined nests, sheets and cords of undifferentiated cells (Figure 1B and 1C) tumour cells have scant cytoplasm, indistinct cell borders and round to oval nuclei. Mitotic figures were numerous, up to five per high power field. Apoptosis and necrosis were prominent. Extensive desmoplastic stroma was present.


Paratesticular desmoplastic small round cell tumour: an unusual tumour with an unusual fusion; cytogenetic and molecular genetic analysis combining RT-PCR and COBRA-FISH.

Cliteur VP, Szuhai K, Baelde HJ, van Dam J, Gelderblom H, Hogendoorn PC - Clin Sarcoma Res (2012)

Macro- and microscopic features. A: gross specimen. The tumour masses were solid, firm, with grey-white cut surfaces and areas of necrosis. B: light micrograph showing compact nests and sheets of small, round cells in desmoplastic stroma. Magnification 25× C: numerous mitotic figures can be observed. Magnification 200× D: Immunohistochemical detection of desmin; the reaction shows a typical paranuclear dot-like staining. Magnification 200×.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3351707&req=5

Figure 1: Macro- and microscopic features. A: gross specimen. The tumour masses were solid, firm, with grey-white cut surfaces and areas of necrosis. B: light micrograph showing compact nests and sheets of small, round cells in desmoplastic stroma. Magnification 25× C: numerous mitotic figures can be observed. Magnification 200× D: Immunohistochemical detection of desmin; the reaction shows a typical paranuclear dot-like staining. Magnification 200×.
Mentions: Sections obtained from the testicular tumour mass (Figure 1A) were composed of sharply defined nests, sheets and cords of undifferentiated cells (Figure 1B and 1C) tumour cells have scant cytoplasm, indistinct cell borders and round to oval nuclei. Mitotic figures were numerous, up to five per high power field. Apoptosis and necrosis were prominent. Extensive desmoplastic stroma was present.

Bottom Line: The EWSR1-WT1 chimera seems to function as an oncogenic transcription factor.Here the zinc finger domain of the WT1 acts with affinity with certain promoter domains influencing the expression of various downstream proteins such as: PDGFA, PAX2, insulin-like growth factor 1 receptor, epidermal growth factor receptor, IL2 receptor beta, BAIAP3, MLF1, TALLA-1, LRRC15 and ENT.We discuss their potential oncogenic roles and potential therapeutic consequences.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pathology, Leiden University Medical Center, Leiden, Albinusdreef 2, Leiden, The Netherlands. P.C.W.Hogendoorn@lumc.nl.

ABSTRACT
Desmoplastic small round cell tumour is a rare malignant tumour with a male to female ratio of 4:1. It manifests mostly at serosal sites. Here we present a case of a 28-year-old male patient, who presented with a fast growing paratesticular mass. On biopsy nests and cords of small round cells, without a clear morphological lineage of differentiation were seen. Occasionally desmoplatic small round cell tumour shows different lines of differentiation. An unequivocal histological diagnosis might be difficult in such cases. Here we demonstrate by a combination of methods the characteristic immunohistochemical profile and - albeit unusual - molecular background and discuss the eventual link with Ewing sarcoma.Immunohistochemical studies showed a membranous staining of Keratine AE1/3 and a dot-like staining of Desmine, confirming its diagnosis. Using COBRA-FISH following a metaphase approach we demonstrated a balanced translocation, t(11;22)(p13;q12) and in RT-PCR formation of the EWSR1-WT1 fusion product, a specific translocation of desmoplastic round cell tumour. The fusion involves exon 9 of EWSR1 to exon 8 of WT1, an unusual fusion product, though earlier described in a case of a desmoplastic small round cell tumour of the hand. The EWSR1-WT1 chimera seems to function as an oncogenic transcription factor. Here the zinc finger domain of the WT1 acts with affinity with certain promoter domains influencing the expression of various downstream proteins such as: PDGFA, PAX2, insulin-like growth factor 1 receptor, epidermal growth factor receptor, IL2 receptor beta, BAIAP3, MLF1, TALLA-1, LRRC15 and ENT. We discuss their potential oncogenic roles and potential therapeutic consequences.

No MeSH data available.


Related in: MedlinePlus