Skin of Patients with Large/Giant Congenital Melanocytic Nevi Shows Increased Mast Cells

Salgado, Cláudia; Silver, Randi B.; Bauer, Bruce S.; Basu, Dipanjan; Schmitt, Lori; Khakoo, Yasmin; Reyes‐Múgica, Miguel

doi:10.2350/14-02-1444-oa.1

Cited by 14 publications

(7 citation statements)

References 30 publications

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“…The number of tryptase + and chymase + mast cells is typically increased in skin diseases involving inflammatory cells, such as in psoriasis and basal cell carcinoma, compared with the corresponding healthy skin of the same patients [20,24]. A high density of cutaneous mast cells has also been found in patients with large congenital melanocytic nevi compared with control individuals without nevi [25]. Recently, increased tryptase + mast cell counts were found in the healthy skin of tobacco smokers [26].…”

Section: Discussionmentioning

confidence: 95%

Low numbers of tryptase+ and chymase+ mast cells associated with reduced survival and advanced tumor stage in melanoma

Siiskonen

Poukka

Bykachev³

et al. 2015

Melanoma Research

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The role of mast cells in cutaneous melanoma remains unclear. Tryptase and chymase are serine proteinases and major proteins in mast cell secretory granules. Therefore, this study aimed to investigate the presence of tryptase and chymase mast cells in benign and malignant cutaneous melanocytic lesions and in lymph node metastases of melanomas. The presence of positively stained mast cells was correlated with clinicopathological characteristics in invasive melanomas. Paraffin-embedded sections of 28 benign (13 intradermal, 10 compound, and five junctional nevi) and 26 dysplastic nevi, 15 in-situ melanomas, 36 superficially (pT1, Breslow's thickness<1 mm), and 49 deeply (pT4, Breslow's thickness>4 mm) invasive melanomas and 30 lymph node metastases were immunohistochemically stained for mast cell tryptase and chymase, and immunopositive cells were counted using the hotspot counting method. The mean count of tryptase and chymase mast cells was lower in invasive melanomas compared with in-situ melanomas and dysplastic and benign nevi. In deeply invasive melanomas, the difference was statistically significant compared with dysplastic nevi (P=0.003 for tryptase and P=0.009 for chymase) and in-situ melanomas (0.043 for tryptase). Low numbers of tryptase mast cells were associated with poor overall survival (P=0.031) in deeply invasive melanomas and with a more advanced stage (T1b, P=0.008) in superficially invasive melanomas. Low numbers of chymase mast cells were associated with microsatellites (P=0.017) in deeply invasive melanomas. The results suggest that these serine proteinases of mast cells may be protective in the pathogenesis of melanoma.

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Section: Discussionmentioning

confidence: 95%

Low numbers of tryptase+ and chymase+ mast cells associated with reduced survival and advanced tumor stage in melanoma

Siiskonen

Poukka

Bykachev³

et al. 2015

Melanoma Research

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“…() described two children who had a capillary malformation under their large CMN, associated with intense pruritus. Chronic itch is often reported by large CMN patients, who also demonstrate significantly higher densities of cutaneous mast cells (Salgado et al., ). Our patient also developed an urticarial rash together with the painful episodes, but no eczematous skin changes nor increased mast cell density in his CMN at the time of biopsy.…”

mentioning

confidence: 99%

Giant congenital melanocytic nevus with vascular malformation and epidermal cysts associated with a somatic activating mutation in BRAF

Etchevers

Rosé²,

Kahle

et al. 2018

Pigment Cell Melanoma Res

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Giant congenital melanocytic nevi may be symptomatically isolated or syndromic. Associations with capillary malformations are exceptional, and development of epidermal cysts has not been described. A 71-year-old patient with a giant congenital melanocytic nevus (CMN) of the lower back, buttocks, and thighs was asymptomatic except for unexpected hemorrhage during partial surgical excision years before. Blunt trauma at age 64 initiated recurrent, severe pain under the nevus; multiple large epidermal cysts then developed within it. Imaging and biopsy showed a large, non-pulsatile venous malformation intermingled with the deep nevus. A low-abundance, heterozygous BRAF c.1799T>A (p.V600E) mutation was present in both gluteal and occipital congenital nevi; additional mutations in NRAS, GNAQ, GNA11, HRAS, or PIK3CA were undetectable. This is the first demonstration of a recurrent BRAF mutation in multiple large congenital nevi from the same individual, confirming that this malformation can have multiple genetic origins. Early constitutive activation of BRAF can therefore cause unusual associations of giant nevi with vascular malformations, indicating that both pigment and endothelial cell physiology may be affected by mosaic RASopathies.

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“…In pathological conditions and tissue repair duration, some factors always cause local tissue fibrosis 61 , 62 . There is a positive trend toward the correlation of mast cell numbers with fibrosis 63 - 66 . Based on the hypothesis above, this phenomenon could be explained by the local stiffness gradient, which should be an important mechanical factor for the recruitment of mast cells.…”

Section: Discussionmentioning

confidence: 88%

An investigation of the distribution and location of mast cells affected by the stiffness of substrates as a mechanical niche

et al. 2018

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The distribution and location of mast cells are closely related to their physiological and pathological functions, such as allergic responses, immunity, and fibrosis, and are used in acupuncture. In this study, the distribution of mast cells in vivo was observed, and mechanical clues for understanding their distribution based on mechanical niches were explored. By toluidine blue staining and immunohistochemical staining, we examined the distribution and location of mast cells in rat skin and found that mast cells are distributed in a spatially nonuniform manner, preferring to locate at regions in the tissue and extracellular matrix with stiffness changes. In vitro experiments for studying the distribution of rat basophilic leukemia (RBL-2H3) mast cell line on poly-di-methyl-siloxane (PDMS) substrates with stiffness variations were performed. It was found that RBL-2H3 cells migrate and tend to remain in the areas with stiffness variations. The present research suggests that changing the stiffness of local tissues may stimulate mast cell recruitment, which may be the method by which some traditional Chinese medicine treatments, such as acupuncture. On the basis of the origin of mast cells and our experimental results, we predict that mast cells exist in tissues that contain permeable capillaries and prefer regions with stiffness changes. We discussed this prediction using examples of specific tissues from some cases.

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Skin of Patients with Large/Giant Congenital Melanocytic Nevi Shows Increased Mast Cells

Cited by 14 publications

References 30 publications

Low numbers of tryptase+ and chymase+ mast cells associated with reduced survival and advanced tumor stage in melanoma

Low numbers of tryptase+ and chymase+ mast cells associated with reduced survival and advanced tumor stage in melanoma

Giant congenital melanocytic nevus with vascular malformation and epidermal cysts associated with a somatic activating mutation in BRAF

An investigation of the distribution and location of mast cells affected by the stiffness of substrates as a mechanical niche

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