This pathology video addresses the historical controversy and diagnostic confusion surrounding two distinct tumors of the skin/soft tissue: the dermal nerve sheath myxoma (DNSM) and cellular neurothekeoma (CN). The presenter advocates for clear terminology, urging avoidance of older confusing names like "neurothekeoma." DNSM is presented as a true S100/Sox10 positive nerve sheath tumor characterized by multi-nodular, hypocellular, myxoid areas containing cords of Schwann cells, typically found on distal extremities and prone to local recurrence. In contrast, CN is a non-neural tumor (S100/Sox10 negative), characterized by cellular, epithelioid/histiocytoid nests, typically found on the upper body and head/neck, and is consistently benign. Multiple examples, including highly atypical CN cases exhibiting pleomorphism and mitotic activity, demonstrate the importance of combining morphology (H&E) with key immunohistochemistry to differentiate CN from malignant melanocytic or sarcomatous mimics.
Dermal Nerve Sheath Myxoma vs. Cellular Neurothekeoma: A Pathology Review
0:00 Terminology Confusion: The tumor dermal nerve sheath myxoma (DNSM) has historically been confused with neurothekeoma and cellular neurothekeoma (CN). The preferred terminology is DNSM (for the myxoid lesion) and CN (for the cellular lesion), as they are unrelated entities.
1:19 Dermal Nerve Sheath Myxoma (DNSM) Morphology: DNSM is typically located in the dermis/sub-Q, exhibiting striking multi-nodularity with pale, myxoid, hypo-cellular nodules divided by fibrous septa.
2:40 DNSM Cellular Features: The cells are plump/epithelioid, suspended in the myxoid background, and tend to clump together in cords or chains.
4:11 Key DNSM Diagnostic Feature: The tumor can exhibit nuclear palisading (similar to a schwannoma), confirming its Schwann cell origin.
4:43 DNSM Immunostains (IHC): DNSM is a true nerve sheath tumor, strongly positive for S100 and Sox10, and often positive for GFAP. Mitoses are usually absent or rare.
5:07 Cellular Neurothekeoma (CN) Introduction: CN exhibits multi-lobularity with fibrous septa, but key areas are cellular, sheet-like, and composed of large, histiocytic/epithelioid cells with pale, delicate chromatin.
8:05 CN Immunostains (IHC): CN is fundamentally negative for S100 and Sox10, indicating it is not a true nerve sheath tumor, despite its name. This is the easiest way to distinguish it from DNSM.
10:40 CN Differential Diagnosis: CN often mimics malignant melanocytic tumors (especially Spitzoid lesions) due to its cellularity, nesting pattern, and presence of mitotic figures (average rate of 3 per 10 HPFs). S100/Sox10 negativity is crucial for exclusion.
12:15 CN Clinical Behavior: Unlike melanocytic lesions, mitotic activity and nuclear atypia in CN do not predict poor prognosis; CN is considered benign.
DNSM: Strong predilection for distal extremities (hands/fingers). Has a significant tendency for local recurrence (can recur 3-5 times or more).
CN: Typically found on the upper extremities (shoulder), head, and neck (often in children/young adults, female predilection). Low risk of recurrence.
18:11 Additional CN Features: A subset of CN (approx. 15%) will feature multinucleated giant cells (osteoclast-like), which is a useful diagnostic clue. CN involvement is restricted to the dermis, not involving the epidermis.
19:47 Mixed Cases: Cases exhibiting both myxoid/hypocellular areas and cellular/sheet-like areas are classified as CN (and are S100/Sox10 negative). Approximately one-third of CNs have myxoid areas.
24:25 Atypical CN Presentation: Highly atypical CNs may exhibit significant pleomorphism, large size, and atypical mitotic figures (26:14), making them difficult to distinguish from malignant mimics like pleomorphic sarcoma or melanoma.
33:50 Key Diagnostic Feature of Atypical CN: In large, atypical CNs, small, classic, non-atypical nests of CN cells can often be found at the tumor periphery, confirming the benign diagnosis despite the aggressive appearance of the main mass.
35:36 Importance of H&E and Caution: H&E morphology is the most important diagnostic tool. When faced with highly atypical CN, conservative excision and close follow-up are recommended due to the rarity and potential for misdiagnosis as malignancy.