Article Evaluation of Melanocyte Loss in Mycosis Fungoides Using SOX10 Immunohistochemistry Cynthia Reyes Barron and Bruce R. Smoller * Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY 14642, USA; [email protected] * Correspondence: [email protected] Abstract: Mycosis fungoides (MF) is a subtype of primary cutaneous T-cell lymphoma (CTCL) with an indolent course that rarely progresses. Histologically, the lesions display a superficial lymphocytic infiltrate with epidermotropism of neoplastic T-cells. Hypopigmented MF is a rare variant that presents with hypopigmented lesions and is more likely to affect young patients. The etiology of the hypopigmentation is unclear. The aim of this study was to assess melanocyte loss in MF through immunohistochemistry (IHC) with SOX10. Twenty cases were evaluated, including seven of the hypopigmented subtype. The neoplastic epidermotropic infiltrate consisted predominantly of CD4+ T-cells in 65% of cases; CD8+ T-cells were present in moderate to abundant numbers in most cases. SOX10 IHC showed a decrease or focal complete loss of melanocytes in 50% of the cases. The predominant neoplastic cell type (CD4+/CD8+), age, race, gender, histologic features, and reported clinical pigmentation of the lesions were not predictive of melanocyte loss. A significant loss of melanocytes was observed in 43% of hypopigmented cases and 54% of conventional cases. Additional studies will increase our understanding of the relationship between observed pigmentation and the loss of melanocytes in MF. Citation: Barron, C.R.; Smoller, B.R. Evaluation of Melanocyte Loss in Keywords: mycosis fungoides; hypopigmented mycosis fungoides; SOX10; cutaneous T-cell lymphoma Mycosis Fungoides Using SOX10 Immunohistochemistry. Dermatopathology 2021, 8, 277–284. https://doi.org/10.3390/ 1. Introduction dermatopathology8030034 Mycosis fungoides (MF) is the most common subtype of primary cutaneous T-cell Academic Editor: Gürkan Kaya lymphoma and is characterized by the presence of malignant T-cells within the epidermis (epidermotropism) [1]. The neoplastic T-cells often have a phenotype that is CD3 positive, Received: 7 June 2021 CD4 positive, and CD8 negative with a frequent loss of other T-cell markers such as CD5 Accepted: 6 July 2021 and/or CD7 [2]. Clonal T-cell receptor (TCR) gamma gene rearrangements, that may be Published: 8 July 2021 determined by PCR-based amplification and gel electrophoresis, support the diagnosis [2]. MF usually follows an indolent course but may progress from a patch stage to plaque to Publisher’s Note: MDPI stays neutral tumor and disseminated disease [3]. There is generally good clinicopathologic correlation with regard to jurisdictional claims in for these stages of disease and they display distinct findings histologically [4]. Although published maps and institutional affil- mortality is low, MF may undergo large cell transformation with significant reduction in iations. survival [5]. MF is a disease primarily affecting adults, and patients typically present with per- sistent erythematous patches and plaques in skin that is sun protected such as the trunk (see Figure1). However, the presentation may be quite variable and non-specific with a Copyright: © 2021 by the authors. clinical differential including psoriasis and eczema, among others. Multiple biopsies are Licensee MDPI, Basel, Switzerland. often required for diagnosis. Reflectance confocal microscopy, a non-invasive method of This article is an open access article visualizing the skin in horizontal planes, may be a useful tool for initial screening in the distributed under the terms and clinic because the findings correlate well with histologic findings including the identifica- conditions of the Creative Commons tion of epidermotropic lymphocytes [6]. Dermoscopy for the evaluation of inflammatory Attribution (CC BY) license (https:// lesions is also becoming more common and frequent findings in MF include the presence creativecommons.org/licenses/by/ of white scales and predominantly patchy vessel arrangements [7]. The clinical findings, 4.0/). Dermatopathology 2021, 8, 277–284. https://doi.org/10.3390/dermatopathology8030034 https://www.mdpi.com/journal/dermatopathology Dermatopathology 2021, 8 2 Dermatopathology 2021, 8 278 scales and predominantly patchy vessel arrangements [7]. The clinical findings, including includingfeatures observed features observedusing confocal using microscopy confocal microscopy and dermoscopy, and dermoscopy, may help may guide help the guide deci- thesion decision to biopsy. to biopsy. FigureFigure 1.1.Mycosis Mycosis fungoidesfungoides presentingpresenting asas a a scaly, scaly, erythematous erythematous patch patch in in a a Caucasian Caucasian patient. patient. ThereThere areare numerousnumerous subtypes of of MF MF with with di differentfferent clinical clinical presentations presentations adding adding to tothe the diagnostic diagnostic challenge. challenge. These These subtypes subtypes include include pagetoid pagetoid reticulosis, reticulosis, folliculotropic, folliculotropic, poi- poikilodermatous,kilodermatous, bullous, bullous, granulomatous, granulomatous, an andd hypopigmented hypopigmented [8]. [8 ].Hypopigmented Hypopigmented MF MF is isa arare rare variant variant that that is is more more likely likely than than other other types types of of cutaneous T-cell lymphomalymphoma toto affect affect youngyoung patients patients and and patients patients of Africanof African American American or Hispanic or Hispanic descent descent [9,10]. [9,10]. A recent A studyrecent ofstudy Chinese of Chinese patients patients found that found the age that of the patients age of with patients hypopigmented with hypopigmented MF was significantly MF was youngersignificantly than younger for other than variants for withother a variants median ofwith 13.4 a yearsmedian and of these 13.4 patientsyears and had these a good pa- responsetients had to a treatmentgood response [11]. to Clinically, treatment patients [11]. Clinically, present withpatients patches present or plaqueswith patches in sun- or protectedplaques in areas, sun-protected as in other areas, types as of in MF, other but ty thepes lesionsof MF, but have the lighter lesions coloration have lighter than color- the surroundingation than the skin surrounding (see Figure 2skin). There (see mayFigure also 2). be There a mixed may presentation also be a mixed with the presentation presence ofwith both the hypopigmented presence of both and hypopigmented erythematous lesionsand erythematous [11]. The clinical lesions differential [11]. The clinical diagnosis dif- isferential broad and diagnosis includes is vitiligo,broad and pityriasis includes alba, viti post-inflammatoryligo, pityriasis alba, hypopigmentation, post-inflammatory and hy- leprosypopigmentation, [8]. Biopsy and and leprosy histopathologic [8]. Biopsy analysis and histopathologic are imperative inanalysis making are the imperative diagnosis. in makingSOX10 the isdiagnosis. a protein that functions as a transcription factor that is essential to the differentiation of neural crest cells. One of its many functions involves promoting the de- velopment and survival of melanocytes by regulating the expression of multiple genes [12]. An immunohistochemical (IHC) stain with an antibody to the SOX10 protein is widely available in many laboratories and is an important tool for the evaluation of melanocytic lesions. SOX10 strongly stains the nuclei of melanocytes including melanocytes in benign nevi and melanoma [13]. The absence of staining indicates the absence of melanocytes as is seen in depigmented lesions of vitiligo. SOX10 may be a helpful stain in further understanding the etiology of the loss of pigment in hypopigmented MF. Preliminary stud- ies have shown that other melanocyte IHC markers including Melan-A, tyrosinase, stem cell factor receptor (CD117), and microphthalmia-associated transcription factor (MiTF) appear to be diminished in hypopigmented MF [14]. The sensitivity and specificity of Dermatopathology 2021, 8 279 SOX10 for melanocytes may make it a useful stain to further study the pathophysiology of hypopigmentation in this disease. The diagnosis of hypopigmented MF requires clinical observation. Determining whether hypopigmentation results from the loss of the melanin Dermatopathology 2021, 8 3 pigment only or true loss of melanocytes will require an assessment of lesions from both conventional MF and the rare hypopigmented subtype. FigureFigure 2. MycosisMycosis fungoides fungoides presenting presenting as hypopigmented as hypopigmented macules macules and patches andpatches in the upper in the extremity upper of an African American patient. extremity of an African American patient. 2. MaterialsSOX10 andis a protein Methods that functions as a transcription factor that is essential to the dif- ferentiationA search of was neural conducted crest cells. to One identify of its cases many of functions MF with involves a clinical promoting presentation the ofdevel- hy- popigmentationopment and survival in the of pathology melanocytes archives by regulating at the Department the expression of Pathology of multiple and Laboratory genes [12]. MedicineAn immunohistochemical of the University (IHC) of Rochester stain with Medical an antibody Center. Sevento the casesSOX10 that protein were hypopig-is widely mentedavailable clinically in many were laboratories identified and from is Januaryan impo 2010rtant totool March for the 2020.