© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd

J Cutan Pathol 2014: 41: 139–140 doi: 10.1111/cup.12244 John Wiley & Sons. Printed in Singapore

Journal of Cutaneous Pathology

Letter to the Editor

Dermatopathology by the numbers Keywords: cutaneous lymphoma, immunohistochemistry, pathology To the Editor, Analogous to the (American) football field, the skin hosts a dynamic interaction of various immune system players in homeostasis and disease. We have observed that the cluster of differentiation (CD) numbers assigned to immune system participants,1 and used with immunohistochemical stains to identify cells, correspond closely to jersey numbers of football players with analogous roles on the team (Fig. 1).

For example, CD1a, a marker of antigenpresenting cells (Langerhans cells), functions as a player/coach and rarely gets a dirty uniform, as he holds the safest job on the team (perhaps he is often the kicker!). Antigen-presenting cells are critical for play calling (signaling). As quarterbacks or members of the backfield, CD3, 4, 5, 7 and 8 receive signals from the coaching staff (antigen-presenting cells) and call out plays (signal other cells) via cytokines and chemokines. CD5 and CD7 are role players, because

Fig. 1. A) Page from the immunohistochemistry play book. B) CD30-positive lymphocytes, huddled behind the line of scrimmage (dermal–epidermal junction) in a mycosis fungoides with large-cell transformation play.

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Letter to the Editor their expression can be diminished in malignant T-cells, and CD5 can be aberrantly co-expressed by B-cells in chronic lymphocytic leukemia. CD8, the backup quarterback (and a marker of cytotoxic activity), almost always gets into the game and is helpful for evaluating a T-cell infiltrate. A rookie, CD10, is somewhat large (like germinal center cells), awkward and unready to stray far from the bench (the follicular center). It may move away from the germinal center in a follicular malignancy. CD20, the halfback, is a workhorse B-cell stain. CD21 and CD23 are used sparingly on special teams to highlight the follicular dendritic network in suspected follicular lymphomas. CD30, the fullback, is larger than other lymphocytes in the backfield. Diagnostically, CD30 marks enlarged lymphocytes in anaplastic large-cell lymphoma or lymphomatoid papulosis. Although CD31 is versatile, it usually represents the vascular team. CD34, another utility player, marks stem cells, monocytes, endothelial cells and some fibroblasts. Diagnostically, it can be useful in the evaluation of leukemia cutis and dermatofibrosarcoma protuberans. The staining properties of CD43, a utility player, depend upon the context in which it is used. For example, in the setting of a dense dermal mononuclear infiltrate, it may highlight the cells of acute myeloid leukemia or acute myelomonocytic leukemia. In the context of a lymphoplasmacytic infiltrate, it may mark the B-cells of extranodal marginal zone lymphoma. CD45 is always ready to play, mainly on defense, to ensure that one has not missed lymphoma as a possible cause of an infiltrate of dubious origin. A linebacker, CD56, Reference 1. Kurtin PJ. Application of immunohistochemistry in the diagnosis of lymphomatoid lesions. In Lloyd RV, ed. Morphology methods: cell and molecular biology techniques. Totowa: Humana Press, 2001; 277.

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marks natural killer (NK) cells. Unlike cells wearing CD4, NK cells do not check identification (HLA-DR) before attack. CD56-positive cells are implicated in angiocentric lymphomas (nasal/nasal-type NK/Tcell lymphoma) and subcutaneous lymphomas. CD68, a down lineman, works in the trenches and participates in granuloma formation. CD79a, a wide out, is called on to help during third down, when it is unclear whether cells seen are B-cells and is particularly useful when CD20 is injured or unavailable (as with anti-CD20 antibody treatment). CD90, a marker of keratinocyte stem cells, also functions as a down lineman or linebacker by providing pass protection by replenishing injured keratinocytes. The Greeks, namely kappa and lambda, are without numbers because they are not regular members of the team. Only used in special situations, a monotypic aggregation of fraternity brothers portends trouble (meaning a clonal plasma cell population, as seen in marginal zone lymphoma). This represents a brief analogical overview of the immunohistochemistry of dermatopathology as it relates to American football. No doubt this roster will require updating in the future. Who knows what bright young stars (markers) next season will bring? Lawrence E. Gibson, MD1,2 Julia S. Lehman, MD1,2 1 Department of Dermatology Mayo Clinic Rochester, MN, USA, and 2 Department of Laboratory Medicine and Pathology Mayo Clinic Rochester, MN, USA e-mail: [email protected]

Dermatopathology by the numbers.

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