J Cutan Pathol 2015: 42: 228 doi: 10.1111/cup.12398 John Wiley & Sons. Printed in Singapore
© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Journal of Cutaneous Pathology
Letter to the Editor
Reply to letter ‘An old debate, rekindled’ Keywords: acanthoma, actinic keratosis, Bowen disease, seborrheic keratosis, solar lentigo To the Editor , I thank the authors for their insights on the ‘prickly’ problem of large cell acanthoma (LCA). I agree that if LCA is too broadly defined, it may devolve into a mishmash of both benign and early cancerous keratinocytic tumors. In his original description Hermann Pinkus noted that the cells appeared ‘quite normal except for the fact that nuclei as well as cytoplasm are about twice normal size’. Dr. Pinkus further remarked on the absence of poikilokaryosis, dyskeratosis and parakeratosis.1 I report such cases as either benign solar lentigo or macular seborrheic keratosis. To the best of my knowledge, none have progressed to bona fide skin cancers. On the other hand, I often see cases of actinic keratosis and (rarely) Bowen disease with enlarged keratinocytes. Additional cytologic and architectural features other than cell size may be necessary to bring order to what might otherwise be construed as a broad and non-specific group of tumors. The aneuploid cell populations in LCA are a thornier issue. Aneuploidy is usually detrimental to cells and would support the more aggressive
management strategy suggested by the authors. However, aneuploidy is not diagnostic of malignancy, and its measurement may be affected by the mode of detection. For example, until recently aneuploidy was thought to be prevalent in both normal liver and brain cells.2 – 4 Hyperploid keratinocytes in LCA were identified by image analysis of Feulgen-stained sections.5 Feulgen staining measures DNA content rather than karyotype and serves as a surrogate measure of aneuploidy. It would be interesting to revisit this issue with newer technology such as single cell sequencing studies. In summary, I agree with the authors that while most cases of LCA represent solar lentigo and can be reported as such, cases with nuclear atypia, an irregular maturation gradient or aberrant mitoses warrant destruction of any remaining lesion. Garth Fraga, MD Pathology and Laboratory Medicine University of Kansas Hospital Kansas City, KS, USA e-mail: [email protected]
References 1. Pinkus H. Epidermal mosaic in benign and precancerous neoplasia (with special reference to large-cell acanthomas). Hifuka Kiyo 1970; 65: 75. 2. Duncan AW, Taylor MH, Hickey RD, et al. The ploidy conveyor of mature hepatocytes
228
as a source of genetic variation. Nature 2010; 467: 707. 3. Rehen SK, McConnell MJ, Kaushal D, Kingsbury MA, Yang AH, Chun J. Chromosomal variation in neurons of the developing and adult mammalian nervous system. Proc Natl Acad Sci U S A 2001; 98: 13361.
4. Knouse KA, Wu J, Whittaker CA, Amon A. Single cell sequencing reveals low levels of aneuploidy across mammalian tissues. Proc Natl Acad Sci U S A 2014; 111: 13409. 5. Rabinowitz AD, Inghirami G. Large-cell acanthoma: a distinctive keratosis. Am J Dermatopathol 1992; 14: 136.
© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Journal of Cutaneous Pathology
Letter to the Editor
Reply to letter ‘An old debate, rekindled’ Keywords: acanthoma, actinic keratosis, Bowen disease, seborrheic keratosis, solar lentigo To the Editor , I thank the authors for their insights on the ‘prickly’ problem of large cell acanthoma (LCA). I agree that if LCA is too broadly defined, it may devolve into a mishmash of both benign and early cancerous keratinocytic tumors. In his original description Hermann Pinkus noted that the cells appeared ‘quite normal except for the fact that nuclei as well as cytoplasm are about twice normal size’. Dr. Pinkus further remarked on the absence of poikilokaryosis, dyskeratosis and parakeratosis.1 I report such cases as either benign solar lentigo or macular seborrheic keratosis. To the best of my knowledge, none have progressed to bona fide skin cancers. On the other hand, I often see cases of actinic keratosis and (rarely) Bowen disease with enlarged keratinocytes. Additional cytologic and architectural features other than cell size may be necessary to bring order to what might otherwise be construed as a broad and non-specific group of tumors. The aneuploid cell populations in LCA are a thornier issue. Aneuploidy is usually detrimental to cells and would support the more aggressive
management strategy suggested by the authors. However, aneuploidy is not diagnostic of malignancy, and its measurement may be affected by the mode of detection. For example, until recently aneuploidy was thought to be prevalent in both normal liver and brain cells.2 – 4 Hyperploid keratinocytes in LCA were identified by image analysis of Feulgen-stained sections.5 Feulgen staining measures DNA content rather than karyotype and serves as a surrogate measure of aneuploidy. It would be interesting to revisit this issue with newer technology such as single cell sequencing studies. In summary, I agree with the authors that while most cases of LCA represent solar lentigo and can be reported as such, cases with nuclear atypia, an irregular maturation gradient or aberrant mitoses warrant destruction of any remaining lesion. Garth Fraga, MD Pathology and Laboratory Medicine University of Kansas Hospital Kansas City, KS, USA e-mail: [email protected]
References 1. Pinkus H. Epidermal mosaic in benign and precancerous neoplasia (with special reference to large-cell acanthomas). Hifuka Kiyo 1970; 65: 75. 2. Duncan AW, Taylor MH, Hickey RD, et al. The ploidy conveyor of mature hepatocytes
228
as a source of genetic variation. Nature 2010; 467: 707. 3. Rehen SK, McConnell MJ, Kaushal D, Kingsbury MA, Yang AH, Chun J. Chromosomal variation in neurons of the developing and adult mammalian nervous system. Proc Natl Acad Sci U S A 2001; 98: 13361.
4. Knouse KA, Wu J, Whittaker CA, Amon A. Single cell sequencing reveals low levels of aneuploidy across mammalian tissues. Proc Natl Acad Sci U S A 2014; 111: 13409. 5. Rabinowitz AD, Inghirami G. Large-cell acanthoma: a distinctive keratosis. Am J Dermatopathol 1992; 14: 136.
