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S-100 Protein Positivity in Onychomatricoma, a Potential Diagnostic Pitfall?

Perrin, Christophe MD

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The American Journal of Dermatopathology: August 2020 - Volume 42 - Issue 8 - p 622-623
doi: 10.1097/DAD.0000000000001624
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To the editor:

In the 2019 issue of this journal appeared an article about the subject of onychomatricoma (OM) that contented the following sentence: “As we have not found published articles regarding S-100 expression in OM, we have stained 4 OM clear-cut cases from our files”.1 The first portion of the sentence is inaccurate because the immunophenotyping profile of the stroma of OM has been clearly defined since 2010 as a diffuse expression of CD34 and negativity for S-100 protein, EMA, CD99, actin, and desmin on a series of 19 tumors.2

The authors diagnose neurofibroma on the expression of S-100 protein alone. However, S-100 protein expression must be regarded with caution because it does not necessarily represent a marker of nerve sheath tumor as inferred by the long list of benign tumor that expresses this protein, specially intradermal nevus including nevus with neural differentiation. Unfortunately, additional staining as Melan A and HMB45 has not been analyzed in this case report. Indeed, melanocytic lesions have been classically reported associated with cysts, desmoplasic trichoepithelioma, and syringoma.

As this case report shows a deep dermal nodule with fascicles of spindle cells separated by narrow gaps and that neurofilament and epithelial membrane antigen expression is not analyzed, the possibility of a traumatic or even palisaded encapsulated neuroma remains to be ruled out. In my routine practice, I have observed that the stroma of OM occasionally includes preexisting nerves (Fig. 1A), which could be the microanatomic structure responsible of such traumatic like neuroma linked to the repetitive movement of the foot with chronic trauma on the thick nail plate of OM.

FIGURE 1.
FIGURE 1.:
S-100 protein stain (×200); (A) unmyelinated axons surrounded by Schwann cells arranged in a branching network in the stroma of the digitated fibroepithelial projections of OM; (B) spindle- and stellate-shaped cells of OM expressing S-100 protein.

In this case report, the differential diagnosis become more challenging if the authors take into account that an aberrant expression of S-100 protein is well documented in cutaneous scars.3

I have recently encountered such fibroblast immunophenotyping modulation in 2 cases of OM with a thick nail plate, as a scattered or patchy expression of S-100 protein (Fig. 1B). The authors claim that OM shows a horizontally arranged fibroblastic pattern, contrasting to “vertically arranged pattern” of subungual neurofibroma. In fact, the deep portion of the stroma of OM is histopathologically characterized by a cellular proliferation of spindled and stellate-shaped monomorphous cells, arranged in a random, loose storiform, or fascicular growth pattern with a myxocollagenous or collagenous stroma.2 In this way, an aberrant expression of S-100 protein linked to chronic trauma on the thick nail plate of OM could be equally suggested.

To conclude, the present report does not solidly demonstrate a collision of subungual neurofibroma and onychomatricoma.

REFERENCES

1. Llamas-Velasco M, Espinosa P, Ovejero-Merino E, et al. Collision of subungual neurofibroma and onychomatricoma: S100 positivity as a clue. Am J Dermatopathol. 2019;32:1–8.
2. Perrin C, Baran R, Balaguer T, et al. Onychomatricoma: new clinical and histological features. A review of 19 tumors. Am J Dermatopathol. 2010;32:1–8.
3. Chorny JA, Barr RJ. S100-positive spindle cells in scars. Am J Dermatopathol. 2002;24:309–312.
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