Case 36

A 70-year-old female with a prior diagnosis of malignant thigh mass and presented with a lesion in the brain, here is the CSF specimen cell block.

Hint: No IHC will help 100% diagnosis this entity in soft tissue world; However, S100, C-KIT, and neuroendocrine markers are starters before molecular.

1. What is the molecular alteration for this entity?

   A: EWSR-FLI1

   B: STAT6-NAB2

   C: FUS-DDIT3

   D: FUS-CREB

   E: TAF15-NR4A3

   
   

Answer

This is a case of extraskeletal myxoid chondrosarcoma. The correct answer is E. EMC showed either NR4A3 with EWSR1 or TAF15.

Key Features:

1. Architecture & Stroma:

Multinodular structure with fibrous septa dividing hypocellular lobules.

Abundant pale-blue myxoid or chondromyxoid matrix.

Absence of well-formed hyaline cartilage.

Strikingly hypovascular stroma.

b. Cellular Morphology:

Cells form cords, clusters, trabecular, or cribriform patterns.

Cytoplasm is eosinophilic to vacuolated with elongated cytoplasmic processes. Uniform round-to-oval nuclei with evenly distributed chromatin and inconspicuous nucleoli. Low mitotic activity. Rhabdoid cytoplasmic inclusions in some cases. Rare hypercellular variants exhibit higher-grade epithelioid cytomorphology and reduced myxoid matrix.

c. Immunohistochemistry:

• Positive Markers:

• S100 (up to 20% of cases).

• KIT (CD117) (up to 30% of cases).

• Synaptophysin and NSE (in some cases).

• Negative Markers:

• SMARCB1 (INI1) in rhabdoid-featured tumours.

• Rare expression of keratins or GFAP.

• Negative for muscle markers.

Reference: https://tumourclassification.iarc.who.int/chaptercontent/33/125

Case credit: UCSD Pathology

Author: Wangpan Shi