Anatomical pathologyProtein gene product 9.5 (PGP9.5) expression in benign cutaneous mesenchymal, histiocytic, and melanocytic lesions: comparison with cellular neurothekeoma
Introduction
In dermatopathology practice, it is not uncommon to encounter biopsies of benign superficial dermal lesions which are difficult to classify based on histomorphology alone. Cellular neurothekeoma (CNTK) readily enters the differential diagnosis of these lesions owing to its nondescript clinical appearance, histomorphological heterogeneity, and potential to mimic a variety of other dermal-based lesions.1, 2 One of the immunohistochemical markers for CNTK is protein gene product 9.5 (PGP9.5), a neuron-specific ubiquitin C-terminal hydrolase with a primary function in ubiquitin regeneration following intracellular protein degradation.3 This protein is localised in normal neural and neuroendocrine tissues, as well as tumours of neuroendocrine and neuroectodermal origins. While PGP9.5 expression in CNTK seemed to support a former belief that it is a tumour of nerve sheath lineage,4 more recent studies have pointed to a non-neural, possibly fibroblastic/fibrohistiocytic origin.5, 6, 7, 8 The specificity of PGP9.5 for neural or nerve sheath differentiation was also disputed by a previous study which demonstrated PGP9.5 expression in a wide variety of deep soft tissue neoplasms, including malignant peripheral nerve sheath tumour, dermatofibrosarcoma, malignant fibrous histiocytoma, low-grade fibromyxoid sarcoma, angiosarcoma, pleomorphic liposarcoma, rhabdomyosarcoma, synovial sarcoma, and melanoma.9
While PGP9.5 is thought to be of no diagnostic value in deep soft tissue neoplasms, little data is available on PGP9.5 expression in benign dermal-based lesions other than CNTK, especially those that may potentially mimic the latter. Distinction of CNTK from other benign dermal-based lesions is important as conservative excision is often performed for CNTK to avoid local recurrence upon incomplete excision,10, 11 while no treatment is usually needed for most of its benign mimics. Due to the lack of more specific markers for CNTK described to date, PGP9.5 remains one of the frequently used antibodies in confirming a diagnosis of CNTK. Therefore, its utility in dermatopathology practice warrants better characterisation. Herein we aimed to determine the specificity of PGP9.5 by examining its expression in a wide spectrum of benign dermal mesenchymal, histiocytic, and melanocytic lesions, in order to provide useful information on the utilisation, interpretation, and potential pitfalls of this antibody.
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Materials and methods
This study was approved by the Institutional Review Boards at University of Michigan and Massachusetts General Hospital. The surgical pathology archive at University of Michigan was searched for the following: ‘cellular neurothekeoma’, ‘schwannoma’, ‘palisaded encapsulated neuroma’, ‘granular cell tumor’, ‘neurofibroma’, ‘plexiform fibrohistiocytic tumor’, ‘fibrous papule’, ‘pleomorphic fibroma’, ‘myxoma’, ‘superficial acral fibromyxoma’, ‘trichofolliculoma’, ‘fibrofolliculoma’, ‘Rosai–Dorfman
Results
The final cohort consisted of 134 cases categorised as cellular neurothekeoma (n = 7), neural/nerve sheath lesions (n = 28), fibrohistiocytic lesions (n = 23), fibroblastic lesions (n = 25), histiocytic lesions (n = 18), myofibroblastic lesions (n = 7), smooth muscle lesions (n = 14), and melanocytic lesions (n = 12) based on their presumed lineage of differentiation. The mean H-scores and the p values from comparison with the CNTK group are summarised in Table 1. Representative examples from all examined
Discussion
Cellular neurothekeoma is a benign dermal neoplasm most commonly occurring on the head and neck and upper limbs of young adults.5, 10 Classically, CNTK forms a fairly well circumscribed dermal papule or nodule consisting of nests of bland epithelioid to spindle cells separated by collagenous bands. However, CNTK may also exhibit different growth patterns and morphological variants which may be easily confused with other dermal-based mesenchymal, histiocytic and melanocytic lesions.1, 2 To add
Acknowledgements
Presented at the 52nd Annual Meeting of the American Society of Dermatopathology, San Francisco, CA, USA, October 8–11, 2015. The authors would like to thank Tina Fields (Research Histology and Immunohistochemistry Laboratory, Comprehensive Cancer Center, University of Michigan) for her help with immunohistochemistry.
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