Correspondence J. Kenneth Schoolmeester, MD Department of Laboratory Medicine and Pathology, Mayo Clinic Rochester, MN 55905 Department of Pathology, Johns Hopkins Hospital, Baltimore, MD E-mail: [email protected]
Ricardo R. Lastra, MD Department of Pathology, Johns Hopkins Hospital Baltimore, MD http://dx.doi.org/10.1016/j.humpath.2015.04.004
References  Chamberlain BK, McClain CM, Gonzalez RS, Coffin CM, Cates JM. Alveolar soft part sarcoma and granular cell tumor: an immunohistochemical comparison study. HUM PATHOL 2014;45:1039-44.  Argani P, Lal P, Hutchinson B, Lui MY, Reuter VE, Ladanyi M. Aberrant nuclear immunoreactivity for TFE3 in neoplasms with TFE3 gene fusions: a sensitive and specific immunohistochemical assay. Am J Surg Pathol 2003;27:750-61.  Hodge JC, Pearce KE, Wang X, Wiktor AE, Oliveira AM, Greipp PT. Molecular cytogenetic analysis for TFE3 rearrangement in Xp11.2 renal cell carcinoma and alveolar soft part sarcoma: validation and clinical experience with 75 cases. Mod Pathol 2014;27:113-27.
1243 alveolar soft part sarcomas, and perivascular epithelioid cell neoplasms). They further suggest that genetic alterations other than TFE3 translocation may explain the presence of nuclear TFE3 in granular cell tumors. In addition to this plausible hypothesis, we wish to propose another for consideration. TFE3 is instrumental in feedback regulation of lysosome/phagosome synthesis and the Golgi stress response [2–4] and may induce the characteristic cytoplasmic accumulation of phagolysosomes in granular cell tumors and other TFE3-related tumors. Conversely, aberrant nuclear TFE3 accumulation in granular cell tumor may be the result of dysfunctional organellar or intracellular metabolic signaling pathways, such as deregulated lysosomal– mammalian target of rapamycin signaling [2,5]. Benjamin K. Chamberlain, MD Colt M. McClain, MD Raul S. Gonzalez, MD Cheryl M. Coffin, MD Justin M. Cates, MD, PhD Department of Pathology, Vanderbilt University Medical Center, Nashville, TN 37232 E-mail address: [email protected]
Granular cell tumors overexpress TFE3 without corollary gene rearrangement—Reply
To the Editor, In their recent correspondence, Drs Schoolmeester and Lastra demonstrate, as we and others have observed , that most granular cell tumors show nuclear immunoreactivity for the MiTF/TFE family transcription factor TFE3. Furthermore, they show that granular cell tumors lack detectable Xp11.2 rearrangements by fluorescence in situ hybridization, in contrast to other tumors with strong nuclear TFE3 expression (such as Xp11.2 renal cell carcinomas,
References  Chamberlain BK, McClain CM, Gonzalez RS, Coffin CM, Cates JM. Alveolar soft part sarcoma and granular cell tumor: an immunohistochemical comparison study. HUM PATHOL 2014;45:1039-44.  Roczniak-Ferguson A, Petit CS, Froehlich F, et al. The transcription factor TFEB links mTORC1 signaling to transcriptional control of lysosome homeostasis. Sci Signal 2012;5:ra42.  Martina JA, Diab HI, Li H, Puertollano R. Novel roles for the MiTF/TFE family of transcription factors in organelle biogenesis, nutrient sensing, and energy homeostasis. Cell Mol Life Sci 2014;71:2483-97.  Taniguchi M, Nadanaka S, Tanakura S, et al. TFE3 is a bHLH-ZIP–type transcription factor that regulates the mammalian Golgi stress response. Cell Struct Funct 2015;40:13-30.  Martina JA, Diab HI, Lishu L, et al. The nutrient-responsive transcription factor TFE3 promotes autophagy, lysosomal biogenesis, and clearance of cellular debris. Sci Signal 2014;7:ra9.