This pathology session details a challenging case of a subcutaneous trunk mass in an adult, illustrating the difficulty in diagnosing spindle cell neoplasms with highly diverse and disparate morphologies. The tumor displayed features mimicking multiple entities, including hypocellular fascicles, areas resembling neurofibroma and fibrohistiocytic tumors, prominent collagen bundles (described as "ramen noodles"), and fat entrapment reminiscent of dermatofibrosarcoma protuberans (DFSP). Immunostaining revealed a critical profile: CD34 positive, patchy tumor-specific S100 expression, and Sox10 negative, arguing against a traditional neural tumor. These mixed features pointed toward the relatively new and emerging entity: NTRK rearranged spindle cell neoplasm. The discussion emphasizes the use of pan-TRK immunohistochemistry as a screening tool, noting that tumor behavior (low-grade vs. sarcoma) tends to correlate with morphology, and confirmation via molecular testing (FISH) is crucial for identifying specific fusions suitable for targeted therapies.
0:00:40 Challenging Case: The speaker introduces a subcutaneous trunk mass, noting it is perhaps the most challenging case in the series due to its highly disparate and varied morphologies across multiple slides.
0:01:23 Diverse Morphology: The tumor exhibits multiple patterns, including short fascicles of plump cells with prominent collagen, slight pleomorphism, and hypocellularity. The speaker uses the term "juicy" (plump, fat) to describe the cell cytology.
0:03:38 Neural Mimicry: Areas show bundles of "ropey" or "wavy" collagen (likened to ramen noodles), giving a false neural feel.
0:04:01 DFSP-like Features: One area showed fat entrapment resembling Dermatofibrosarcoma Protuberans (DFSP); however, the cytology was too plump, as typical DFSP cells are thin and stretched out.
0:04:46 Multiple Differential Diagnoses: Other areas resemble neurofibroma (S-shaped cells in a mixoid/collagen background) and fibrohistiocytic lesions (plump histiocytoid cells in a storyform pattern).
0:05:27 Immunoprofile Clues: The tumor demonstrated an unusual IHC profile: positive for CD34 and patchy, real tumor-specific expression of S100.
0:06:07 Sox10 Negativity: The tumor was Sox10 negative, which is key in ruling out classic neural tumors or melanocytic lesions, as S100 positivity can sometimes be caused by background dendritic cells.
0:06:30 Diagnosis of Emerging Entity: The combination of features is consistent with an NTRK rearranged spindle cell neoplasm, an emerging entity that currently serves as a broad category.
0:07:36 Behavior Correlates with Morphology: In this group of tumors, if the tumor looks low grade, it likely behaves well; if it looks high grade (sarcoma-like), it will likely behave aggressively, regardless of the NTRK abnormality.
0:07:51 Clinical Utility: Pan-TRK immunohistochemistry can be used as a screening test for NTRK fusions (NTRK 1, 2, or 3), followed by molecular testing (0:08:01). This knowledge is crucial for identifying targeted therapies for malignant cases (0:08:34).
0:09:29 Complexity of NTRK Staining: A colleague notes that the Pan-TRK staining pattern can be complex and sometimes correlate with the specific fusion partner (the 5-prime partner). For example, ETV6 NTRK3 fusions often show nuclear staining, while MYO5A NTRK3 fusions may show cytoplasmic staining.
0:12:10 Pan-TRK Sensitivity Variation: Pan-TRK sensitivity varies by subtype: NTRK1 fusions are typically very strong, but NTRK3 fusions require careful scrutiny, often needing FISH confirmation due to weak or unreliable IHC staining.