Abstract
Mycosis fungoides with large cell transformation (MFLCT) can be difficult to distinguish from primary cutaneous CD30+ T cell lymphoproliferative disorders (PC CD30+ LPD), especially primary cutaneous anaplastic large cell lymphoma (PC-ALCL). This diagnostic distinction is critical for appropriate patient management. GATA3 has been proposed to be useful in the discrimination between these two entities. We identified 25 cases of MFLCT and 24 cases of PC CD30+ LPDs (including lymphomatoid papulosis (n=14), PC-ALCL (n=6), and CD30+ LPD, not otherwise specified (n=4)) diagnosed at our institution from 2002 to 2019. Sections from archived specimens were stained to evaluate for GATA3 expression by immunohistochemistry and compared among cutaneous CD30+ T cell LPDs. The majority of the MFLCT cohort had strong, diffuse expression of GATA3 ranging from 0 to 100% of dermal T cells (mean 53.20%) with 15/25 cases (60%) showing GATA3 expression greater than 50%, while the PC CD30+ LPD group showed variable, moderate GATA3 labeling ranging from 0 to 60% of dermal T cells (mean 23.26%), with 5/6 cases (83%) showing GATA3 expression less than 40% (p =0.003). The calculated sensitivity and specificity were 56% and 74%, while positive and negative predictive values were 70% and 61%, respectively. Based on the percent staining of positive cells, using 50% as a cutoff value for expression, GATA3 might be a useful immunohistochemical marker to discriminate MFLCT from PC CD30+ LPDs, including PC-ALCL.
Similar content being viewed by others
References
Robson A (2007) The pathology of cutaneous T-cell lymphoma. Oncology. 21(2):9–12
Diamandidou E, Colome-Grimmer M, Fayad L, Duvic M, Kurzrock R (1998) Transformation of mycosis fungoides/Sezary syndrome: clinical characteristics and prognosis. Blood. 92(4):1150–1159
Benner MF, Jansen PM, Vermeer MH, Willemze R (2012) Prognostic factors in transformed mycosis fungoides: a retrospective analysis of 100 cases. Blood. 119(7):1643–1649
Ally MS, Robson A (2014) A review of the solitary cutaneous T-cell lymphomas. J Cutan Pathol 41(9):703–714
Paulli M, Berti E, Rosso R, Boveri E, Kindl S, Klersy C, Lazzarino M, Borroni G, Menestrina F, Santucci M (1995) CD30/Ki-1-positive lymphoproliferative disorders of the skin— clinicopathologic correlation and statistical analysis of 86 cases: a multicentric study from the European Organization for Research and Treatment of Cancer Cutaneous Lymphoma Project Group. J Clin Oncol 13(6):1343–1354
Wieser I, Oh CW, Talpur R, Duvic M (2016) Lymphomatoid papulosis: treatment response and associated lymphomas in a study of 180 patients. J Am Acad Dermatol 74(1):59–67
Hsi AC, Lee SJ, Rosman IS, Carson KR, Kelley A, Viele V, Pang X, Musiek A, Schaffer A (2015) Expression of helper T cell master regulators in inflammatory dematoses and primary cutaneous T-cell lymphomas: diagnostic implications. J Am Acad Dermatol 72(1):159–167
Kodama K, Fink-Puches R, Massone C, Kerl H, Cerroni L (2005) Papular mycosis fungoides: a new clinical variant of early mycosis fungoides. J Am Acad Dermatol 52(4):694–698
Kadin ME, Hughey LC, Wood GS (2014) Large-cell transformation of mycosis fungoides-differential diagnosis with implications for clinical management: a consensus statement of the US cutaneous lymphoma consortium. J Am Acad Dermatol 70(2):374–376
Kadin ME (2015) CD30-rich transformed mycosis fungoides or anaplastic large cell lymphoma? How to get it right. Br J Dermatol 172(6):1478–1479
Pulitzer M, Myskowski PL, Horwitz SM, Querfeld C, Connolly B, Li J, Murali R (2014) Mycosis fungoides with large cell transformation: clinicopathological features and prognostic factors. Pathology. 46(7):610–616
Romero M, Haney M, Desantis E, Zlotoff B (2008) Mycosis fungoides with focal CD 30 transformation in an adolescent. Pediatr Dermatol 25(5):565–568
Wu H, Telang GH, Lessin SR, Vonderheid EC (2000) Mycosis fungoides with CD30-positive cells in the epidermis. Am J Dermatopathol 22(3):212–216
Mehra T, Ikenberg K, Moos RM, Benz R, Nair G, Schanz U, Haralambieva E, Hoetzenecker W, Dummer R, French LE, Guenova E, Cozzio A (2015) Brentuximab as a treatment for CD30+ mycosis fungoides and Sézary syndrome. JAMA Dermatol 151(1):73–77
Ohtani T, Kikuchi K, Koizumi H, Kunii T, Aiba S (2009) A case of CD30+ large-cell transformation in a patient with unilesional patch-stage mycosis fungoides. Int J Dermatol 48(6):623–626
Fauconneau A, Pham-Ledard A, Cappellen D, Frison E, Prochazkova-Carlotti M, Parrens M, Dalle S, Joly P, Viraben R, Franck F, Ingen-Housz-Oro S, Giacchero D, Jullié ML, Vergier B, Merlio JP, Beylot-Barry M (2015) Assessment of diagnostic criteria between primary cutaneous anaplastic large-cell lymphoma and CD30-rich transformed mycosis fungoides; a study 66 cases. Br J Dermatol 172(6):1547–1554
Jour G, Aung PP, Merrill ED, Curry JL, Tetzlaff MT, Nagarajan P, Ivan D, Prieto VG, Duvic M, Miranda RN, Torres-Cabala CA (2018 Jan) Differential expression of CCR4 in primary cutaneous gamma/delta (γ/δ) T cell lymphomas and mycosis fungoides: significance for diagnosis and therapy. J Dermatol Sci 89(1):88–91
Elbendary A, Parikh K, Ellattar I, Troung J, Elston DM (2016) Expression of T-bet and GATA-3 in early mycosis fungoides and spongiotic dermatitis. J Am Acad Dematol 74(5):1012–1014
Zhu J (2010) Transcriptional regulation of Th2 cell differentiation. Immunol Cell Biol 88(3):244–249
Amador C, Greiner TC, Heavican TB (2019) Reproducing the molecular subclassification of peripheral T-cell lymphoma-NOS by immunohistochemistry. Blood. 134(24):2159–2170
Wang T, Feldman AL, Wada DA, Lu Y, Polk A, Briski R, Ristow K, Habermann TM, Thomas D, Ziesmer SC, Wellik LE, Lanigan TM, Witzig TE, Pittelkow MR, Bailey NG, Hristov AC, Lim MS, Ansell SM, Wilcox RA (2014) GATA-3 expression identified a high-risk subset of PTCL, NOS with distinct molecular and clinical features. Blood. 123(19):3007–3015
Murga-Zamalloa C, Wilcox RA (2020) GATA-3 in T-cell lymphoproliferative disorders. IUMBMB Life 72(1):170–177
McGirt LY, Degesys CA, Johnson VE, Zic JA, Zerner JP, Eischen DM (2016) TOX expression and role in CTCL. J Eur Acad Dermaol Venereol 30(9):1497–1502
Morimura S, Sugaya M, Suga H, Miyagaki T, Ohmatsu H, Fujita H, Asano Y, Tada Y, Kadono T, Sato S (2014) TOX expression in different subtypes of cutaneous lymphoma. Arch Dermatol Res 306(9):843–849
Wan YY (2014) GATA3: A master of many trades in immune regulation. Trends Immunol 35(6):233–242
Acknowledgements
We thank Rachel Christiansen for her critical review of the manuscript. The skillful photographic assistance of Kim-Anh Vu is gratefully acknowledged.
Funding
Funding is provided by The N. Allen and Barbara B. Kannapell Fund for Melanoma Medical Oncology Research.
Author information
Authors and Affiliations
Contributions
All authors contributed to the study conception and design.
Conceptualization: Katrina Collins, Jun Gu, Phyu P Aung, Priyadharsini Nagarajan, Jonathan L Curry, Auris Huen, Doina Ivan, Victor G Prieto, Michael T Tetzlaff, Madeleine Duvic, Roberto N Miranda, Francisco Vega, Carlos A. Torres-Cabala. Methodology: Katrina Collins, Jun Gu, Phyu P Aung, Priyadharsini Nagarajan, Jonathan L Curry, Auris Huen, Doina Ivan, Victor G Prieto, Michael T Tetzlaff, Madeleine Duvic, Roberto N Miranda, Francisco Vega, Carlos A. Torres-Cabala. Formal analysis and investigation: Katrina Collins, Jun Gu, Phyu P Aung, Roberto N Miranda, Francisco Vega, Carlos A. Torres-Cabala. Writing—original draft preparation: Katrina Collins, Roberto N Miranda, Francisco Vega, Carlos A. Torres-Cabala. Writing—review and editing: Katrina Collins, Jun Gu, Phyu P Aung, Priyadharsini Nagarajan, Jonathan L Curry, Auris Huen, Doina Ivan, Victor G Prieto, Michael T Tetzlaff, Madeleine Duvic, Roberto N Miranda, Francisco Vega, Carlos A. Torres-Cabala. Funding acquisition: Francisco Vega, Carlos A. Torres-Cabala. Resources: Katrina Collins, Jun Gu, Francisco Vega, Carlos A. Torres-Cabala. Supervision: Jun Gu, Phyu P Aung, Roberto N Miranda, Francisco Vega, Carlos A. Torres-Cabala
Corresponding author
Ethics declarations
Ethics approval
The study has been conducted according to the guidelines of the local ethical committee.
Conflict of interest
The authors declare no conflict of interest.
Additional information
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Collins, K., Gu, J., Aung, P.P. et al. Is immunohistochemical expression of GATA3 helpful in the differential diagnosis of transformed mycosis fungoides and primary cutaneous CD30-positive T cell lymphoproliferative disorders?. Virchows Arch 479, 377–383 (2021). https://doi.org/10.1007/s00428-021-03056-y
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00428-021-03056-y