Diagnosing Disorders of Hypopigmentation and Depigmentation in Patients with Skin of Color.

Skin hypopigmentation and depigmentation disorders are a top concern for patients with skin of color seeking care from a dermatologist. The visual contrast between involved and uninvolved skin in these disorders makes them particularly burdensome for patients with skin of color. These disorders may have a wide differential of diagnosis, as patients with skin of color may present differently or more frequently than White patients for certain conditions. Clues from a comprehensive history and physical examination with standard lighting and a Wood's light are essential for clinching the diagnosis, although a biopsy may be warranted in special cases.

Basement membrane thickness helps to differentiate hypopigmented mycosis fungoides from clinical and pathological mimickers.

BACKGROUND: Hypopigmented mycosis fungoides (HMF) is a relatively rare subtype of mycosis fungoides (MF). The diagnosis of HMF can be quite challenging in case of insufficient diagnostic criteria due to the diverse conditions that present with hypopigmented lesions. This study aimed to evaluate the usefulness of the assessment of the basement membrane thickness (BMT) in the diagnosis of HMF. METHODS: A retrospective study was conducted on biopsy specimens of 21 HMF and 25 non-HMF cases who presented with hypopigmented lesions. The thickness of the basement membrane was evaluated in periodic acid-Schiff (PAS)-stained sections. RESULTS: The mean BMT was significantly higher in the HMF group than in the non-HMF group (P < 0.001). The best cut-off value of mean BMT for the detection of HMF verified in ROC analysis was 32.7 µm (P < 0.001) with a sensitivity of 85.7% and a specificity of 96%. CONCLUSION: Evaluation of BMT can be a useful tool to distinguish HMF from other causes of hypopigmented lesions in doubtful cases. We suggest the use of " BMT more than 33 µm" as a histopathologic criterion of HMF.

Adolescent extra-truncal progressive macular hypomelanosis.

Two adolescent females presented to outpatient clinic with isolated, non-scaly, asymptomatic hypopigmented macules and patches on the arm(s). Both cases had Wood's lamp exams notable for extralesional punctiform coral-red perifollicular fluorescence on the back and faint intralesional enhancement. In one case, biopsy was performed and deemed consistent with progressive macular hypomelanosis. The patient had complete response to antimicrobial therapy and sun exposure.

Unveiling idiopathic guttate hypomelanosis: pathology, immunohistochemistry, and ultrastructural study.

BACKGROUND: Idiopathic guttate hypomelanosis (IGH) is a pigment disorder of unknown etiology. Despite its high prevalence and the unaesthetic appearance of the lesions, there are relatively few histological studies on this disorder. This is an important gap to understanding its pathogenesis. OBJECTIVES: To assess the microscopic structure of IGH lesions compared to normal adjacent skin areas and the possible interaction between melanocytes and the subjacent dermis. METHODS: In this cross-sectional study, we took biopsy specimens of hypochromic lesions and adjacent normal skin from 20 patients with IGH. We analyzed the fragments using routine stains, immunohistochemistry, and electron microscopy. RESULTS: We found superficial dermal fibrosis in 90% (18/20) of our IGH cases and unreported keratinocyte cytoplasmic changes on electron microscopy. CONCLUSION: Our results suggest an interaction between melanocytes and the subjacent dermis in IGH. These findings can help to understand melanocyte biology and the pathogenesis of other achromic lesions.

De novo mutation in KITLG gene causes a variant of Familial Progressive Hyper- and Hypo-pigmentation (FPHH).

Familial Progressive Hyper- and Hypopigmentation is a pigmentary disorder characterized by a mix of hypo- and hyperpigmented lesions, café-au-lait spots and hypopigmented ash-leaf macules. The disorder was previously linked to KITLG and various mutations have been reported to segregate in different families. Furthermore, association between KITLG mutations and malignancies was also suggested. Exome and SANGER sequencing were performed for identification of KITLG mutations. Functional in silico analyses were additionally performed to assess the findings. We identified a de novo mutation in exon 4 of KITLG gene causing NM_000899.4:c.[329A>T] (chr12:88912508A>T) leading to NP_000890.1:p.(Asp110Val) substitution in the 3rd alpha helix. It was predicted as pathogenic, located in a conserved region and causing an increase in hydrophobicity in the KITLG protein. Our findings clearly confirm an additional hot spot of KITLG mutations in the 3rd alpha helix, which very likely increases the risk of malignancies. To our knowledge the present study provides the strongest evidence of association of the KITLG mutation with both Familial Progressive Hyper- and Hypopigmentation and malignancy due to its' location on somatic cancer mutation locus. Additionally we also address difficulties with classification of the unique phenotype and propose a subtype within broader diagnosis.

Amyloidosis cutis dyschromica cases caused by GPNMB mutations with different inheritance patterns.

BACKGROUND: Amyloidosis cutis dyschromica (ACD) is a rare form of primary cutaneous amyloidosis featured by reticulate dotted hypo- and hyperpigmentation. Recently, loss-of-function mutations in GPNMB, encoding glycoprotein (transmembrane) nonmetastatic melanoma protein B, were found in autosomal-recessive or semi-dominant ACD. OBJECTIVE: This study aims to detect the genetic defect underlying ACD in nine separate cases and to investigate the functional consequences of the mutants. METHODS: Nine ACD cases were collected including eight with autosomal-recessive pattern and one with autosomal-dominant pattern. Whole-exome sequencing or Sanger sequencing of the GPNMB gene was performed to detect the pathogenic mutations. Haplotype analysis was employed to determine the origin of mutation c.565C > T using adjacent highly polymorphic SNPs. Immunoblotting and subcellular localization assessments were performed to evaluate the expression of the mutants using HEK293 cells transfected with the GPNMB constructs. RESULTS: We detected four recurrent mutations (c.393 T > G, p.Y131*; c.565C > T, p.R189*; c.1056delT, p.P353Lfs*20; c.1238 G > C, p.C413S) and two novel mutations (c.935delA, p.N312Tfs*4; c.969 T > A, p.C323*) in GPNMB. Mutation c.565C > T found in six separate ACD cases shared a common haplotype. The two novel mutations caused a decreased abundance of truncated proteins. The c.1238 G > C mutation, which was detected in the autosomal-dominant case, caused abnormal reticular subcellular localization of the protein. A major percentage of wildtype changed its expression pattern when co-expressed with this mutant. CONCLUSIONS: Our findings proved that the recurrent mutation c.565C > T originated from a founder effect. The autosomal-dominant ACD associated mutation p.C413S played its pathogenic role through a dominant-negative effect on wild-type GPNMB. This study expands the genotype and inherited modes of ACD and improves our understanding of the pathogenesis of this disorder.

Hypopigmented mycosis fungoides mimicking leprosy successfully treated with oral and topical corticosteroids: a new great imitator?

Hypopigmented mycosis fungoides (HMF) is a rare variant of patch stage MF, which is often misdiagnosed. A 35-year-old male presented with non-pruritic white patches on his chest that had been present for 10 years. The patient had previously been treated for leprosy without any improvement. Physical examination showed well-defined multiple hypopigmented patches and macules on the chest, posterior trunk, and gluteus, with some lesions exhibiting anhidrosis and central erythema. The result of sensibility examination was unclear. Slit-skin-smear examination for acid-fast bacilli and anti-phenolic-glycolipid-1 examination were negative. Histopathological examination showed Pautrier microabscesses. The patient was diagnosed with HMF and was treated with 16 mg methylprednisolone b.i.d., topical application of desoximetasone, and 1% methoxsalen lotion followed by sun exposure. A significant improvement was observed during the following 6 months. This case shows that HMF needs to be considered in patients presenting with chronic unexplained hypopigmented patches to avoid unnecessary treatment and progression to more advanced stages.

SWEPT-SOURCE OPTICAL COHERENCE TOMOGRAPHY AND OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY FINDINGS IN WAARDENBURG SYNDROME.

PURPOSE: Waardenburg syndrome (WS) is a rare condition characterized by six main features. It has been previously observed that WS is also associated with hypopigmentation of the choroid through multimodal imaging. To our knowledge, this is the first report of using swept-source optical coherence tomography angiography (OCTA) on a patient with known WS. METHODS: Report of a single case. The swept-source OCT images were captured using Topcon DRI OCT Triton (Topcon, Inc, Tokyo, Japan), whereas swept-source OCTA images were captured by Optovue AngioVue (Optovue, Inc, Fremont, CA) using DualTrack Motion Correction Technology. RESULTS: In this case, OCTA demonstrated evidence of normal vasculature of all layers (superficial, deep, and choricocapillaris), a normal foveal avascular zone measuring 0.267 mm2 in the right eye and 0.307 mm2 in the left eye, and a normal capillary density measuring 49.8% in the right eye and 52.6% in the left eye. CONCLUSION: There are many conditions that may mimic the hypopigmentation of the choroid associated with WS; it has been documented that these similar conditions such as choroidal nevus, choroidal melanoma, and Vogt-Koyanagi-Harada syndrome all demonstrated abnormal OCTA findings. Unlike these conditions, our patient with WS had unremarkable OCTA findings.