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Solitary, multiple, benign, atypical, or malignant: the “Granular Cell Tumor” puzzle

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Abstract

The clinical evolution and biology of granular cell tumors (GCT) are poorly understood and treatment remains an issue of discussion. The majority of GCT are benign, although some display malignant behavior. The distinction between benign, atypical, and malignant GCT is controversial due to morphological and immunohistochemical overlap and lack of consistent histological and phenotypic criteria that predict behavior. Although histological criteria may indicate increased risk of malignant evolution, some GCT with evident benign appearance exceptionally progress towards metastatic disease. In this review, we discuss current knowledge on GCT, including histologic, immunophenotypic, and molecular characteristics and differential diagnosis. We focus on the following problematic items in GCT: (1) evolution of classification, (2) neural versus non-neural GCT, (3) neoplastic versus reactive disease, (4) malignant transformation of benign GCT, and (5) multiple versus metastatic GCT. We conclude that although a Ki-67 index >10 % and the presence of mitoses and/or of necrosis are frequently associated with malignant behavior, metastasis remains the only unequivocal sign of malignancy in GCT. An infiltrative growth pattern and vascular and/or perineural invasion are not indicative of malignancy. GCT with atypical/uncertain features almost never metastasize, and many of these tumors either behave in a benign fashion or only recur locally (similar to incompletely excised benign tumors). We therefore propose that classical and atypical histological variants form a single group of GCT. GCT with various unfavorable histological features might be labeled as “GCT with increased risk of metastasis” rather than malignant GCT.

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Acknowledgments

The authors thank David Harrison for the English review and editing of the manuscript.

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Authors and Affiliations

  1. Pathology Department, Instituto Valenciano de Oncología, C/Gregorio Gea 34, 46009, Valencia, Spain

    Isidro Machado & Julia Cruz

  2. Oncology Department, Instituto Valenciano de Oncología, Valencia, Spain

    Javier Lavernia

  3. Pathology Department, University of Valencia, Valencia, Spain

    Antonio Llombart-Bosch

Authors
  1. Isidro Machado
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  2. Julia Cruz
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  3. Javier Lavernia
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  4. Antonio Llombart-Bosch
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Corresponding author

Correspondence to Isidro Machado.

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In the present work, there is no research involving human participants and/or animals. The present study complies with the ethical rules applicable for this journal.

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The authors declare that they have no competing interests.

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Machado, I., Cruz, J., Lavernia, J. et al. Solitary, multiple, benign, atypical, or malignant: the “Granular Cell Tumor” puzzle. Virchows Arch 468, 527–538 (2016). https://doi.org/10.1007/s00428-015-1877-6

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  • DOI: https://doi.org/10.1007/s00428-015-1877-6

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