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Reparative Perineural Hyperplasia and Dermatofibroma

Macarenco, Alessandra C MD; Macarenco, Ricardo S MD

The American Journal of Dermatopathology: June 2010 - Volume 32 - Issue 4 - p 409-410
doi: 10.1097/DAD.0b013e3181b2e14b
Letter to the Editor

*Dermis-Clinica Dermatologica, Sao Jose dos Campos, SP, Brazil; †CIPAX, Medicina Diagnostica, Sao Jose dos Campos, SP, Brazil.

To the Editor:

In the February 2009 issue of this journal, Dr Beer published the original study titled “Reparative perineural hyperplasia: a series of 10 cases.”1 In that study, the author nicely described a series of 10 cutaneous reexcision specimens containing concentric proliferation of perineural cells around nerves in the mid or deep dermis. Such histological alteration occurred in intimate association to fibrosis and/or chronic inflammatory infiltrate. Immunohistochemistry confirmed the perineural differentiation and helped to exclude other processes such as neoplastic perineural invasion and reexcision perineural invasion. The author proposed the term “reparative perineural hyperplasia” (RPH) as a descriptor for this phenomenon.

Recently, we had the opportunity to observe similar findings in association to a dermatofibroma (DF) without history of previous local surgery. A 25-year-old woman sought medical attention for a lump on her right leg of 3-month duration. She denied previous local trauma and was otherwise in a perfect health condition. The attending dermatologist described the lesion as a 0.8-cm nodule over the anterior aspect of the right leg and performed a 4-mm punch biopsy. The microscopic low-power magnification revealed an unencapsulated and well-delimited deep dermal lesion, which spared the superficial dermis (Fig. 1A). Higher power examination showed classic features of DF, including spindle cells with inconspicuous nucleoli, homogeneous chromatin, and barely evident cytoplasm disposed in a slightly storiform collagenous stroma, as well as collagen entrapment in the outer portions of the lesion (Fig. 1B). No necrosis, mitosis, or nuclear atypia were observed. The deepest portion of the DF extended into the subcutaneous fat through the interlobular fibrous septa, toward the deepest margin of the specimen (Figs. 1A, C). At the dermo-hypodermic junction, close to an interlobular fibrous septum, one could observe a nerve entrapped by the main lesion (Fig. 1C). Interestingly, the perineurium of this nerve showed hyperplastic features including ring-like layers of spindle cells harboring plump and hyperchromatic nuclei and with immunoprofile confirmatory of perineurium (EMA+, AE1/AE3, and S100 protein) (Figs. 2A, B). A slight chronic inflammatory infiltrate composed of lymphocytes and plasmocytes was found in adjacent areas to this nerve.





Normal perineurium may present up to 12 concentric cell layers depending on the location and nerve size, and the cells are invariably flattened.2 In nerves of the deep dermis or of the transition between the dermis and the subcutaneous tissue, the perineurium usually has 1-3 concentric layers of thin cells. Although in Dr. Beer's series, the illustrations depict 4-6 cells thick perineurium with slight hyperchromatic nuclei, the present case harbors a 3-4 cells thick perineurium with prominent nuclear enlargement and hyperchromasia. Except for this detail and for the association to DF, these nerve alterations were indistinguishable from the ones described by Dr. Beer in his article.

Despite the fact that the current patient denied previous local trauma, the role of trauma in the pathogenesis of perineural hyperplasia in this case cannot be ruled out for the following reasons: (1) unnoticed minor injuries are likely to occur in the lower leg of any healthy and active person; (2) it occurred in association to a DF, an entity that is widely known (at least a subset of cases) to be related to trauma; and (3) in Dr Beer's series (the only series so far on RPH), all patients had been submitted to cutaneous surgery.

This case illustrates that RPH is not restricted to the context of prior surgical procedure. Indeed, perineural hyperplasia such as the one described here may occur in other fibrosis-associated or trauma-elicited conditions, including cutaneous involvement by systemic sclerosis3 and Morton's neuroma.4 However, to our knowledge its association to a DF has not been noticed in the past.

The importance of recognizing RPH in the current case is to avoid potential misinterpretation of a DF as a peripheral nerve sheath tumor or desmoplastic melanoma. Perhaps, RPH is a phenomenon more common than one would expect, and we believe that from Dr. Beer's study on RPH will be observed more frequently, including in association to other cutaneous conditions related to local trauma or fibrosis.

Alessandra C. Macarenco, MD

Dermis-Clinica Dermatologica, Sao Jose dos Campos, SP, Brazil

Ricardo S. Macarenco, MD

CIPAX-Medicina Diagnostica, Sao Jose dos Campos, SP, Brazil

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1. Beer TW. Reparative perineural hyperplasia: a series of 10 cases. Am J Dermatopathol. 2009;31:50-52.
2. Ortiz-Hidalgo C, Weller RO. Peripheral nervous system. In: Sternberg SS, ed. Histology for Pathologists. 2nd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 1997:285-311.
3. McKee PH, Calonje E, Granter SR. Idiopathic Connective Tissue Disorders.Granter SR. Idiopathic Connective Tissue Disorders. Pathology of the Skin With Clinical Correlations. 3rd ed. London, UK: Elsevier Mosby; 2005:775-836.
4. De Palma L, Tulli A. Morton's disease: optic and electron microscopy observations. Acta Orthop Belg. 1991;57:285-295.
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