Clinical Review & Education
JAMA Dermatology Clinicopathological Challenge
Longitudinal Melanonychia of the Toenail Charlene Lam, MD, MPH; Grace W. Weyant, MD; Elizabeth M. Billingsley, MD
A man in his 60s presented with a pigmented nail streak on the left fourth toenail that had been present for 10 months. He denied pain, tenderness, or trauma. Physical examination revealed a 4-mm wide pigmented streak with varying shades of brown and longitudinal ridging (Figure, A). The nail fold was unin-
A
volved. Because of suspicion for melanoma, a biopsy was recommended. A nail avulsion was performed and demonstrated a 3-mm tan papule beneath the proximal nail fold (Figure, B). The histologic findings are shown in Figure, C. What is your diagnosis?
B
C
Figure. A, Photograph of the left fourth toenail. B, Photograph of the left fourth toenail after nail avulsion. C, Histologic analysis of the tumor (hematoxylin-eosin, original magnification ×10).
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JAMA Dermatology April 2014 Volume 150, Number 4
Copyright 2014 American Medical Association. All rights reserved.
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449
Clinical Review & Education JAMA Dermatology Clinicopathological Challenge
Diagnosis Onychomatricoma (OM)
Microscopic Findings and Clinical Course The tumor was composed of papillomatous epithelium overlying stroma occupied by a collection of cytologically banal spindled cells that expressed CD34 but not epithelial membrane antigen, glucose transporter protein 1, factor XIIIa, S100, and melan-A (Figure, C). Melanocytes were normal in number and distribution as determined by hematoxylin-eosin stain and immunostaining with S100 and melan-A. The tumor was completely excised, and there have been no signs of recurrence for at least 6 months.
Discussion Onychomatricomas were first described by Baran and Kint1 in 1992. They are rare, slow-growing, painless tumors of the nail matrix. Onychomatricoma tends to appear in middle-aged to older individuals, with a possible female predilection.2,3 Fingers are more commonly affected than toes. The etiology of OM is not known, though trauma and onychomycosis have been proposed as associated factors.4,5 A recent genomic analysis of OM demonstrated genomic losses in the tumors.4 The classic clinical presentation involves 4 components: (1) yellow, thickened longitudinal band with prominent ridging on the nail plate; (2) increased transverse overcurvature of the nail; (3) splinter hemorrhages proximally; and (4) a matrical tumor evident after nail avulsion.6 However, there are atypical presentations including melanoncyhia,5 cutaneous horn,2 pterygium, nail bed bleeding, and onychomycosis.2,4 The differential diagnosis includes acquired fibrokeratoma, periungual fibroma, subungual verruca vulgaris, Bowen disease, squamous cell carcinoma, melanoma, fibroepithelioma of Pinkus, ecARTICLE INFORMATION Author Affiliations: Penn State Milton S. Hershey Medical Center, Hershey, Pennsylvania. Corresponding Author: Elizabeth M. Billingsley, MD, Penn State Milton S. Hershey Medical Center, 500 University Dr, Mail Code HU14, Hershey, PA 17033 ([email protected]). Section Editor: Molly A. Hinshaw, MD; Assistant Section Editors: Soon Bahrami, MD; Nicole Fett, MD, MSCE; Anna K. Haemel, MD; Arni K. Kristjansson, MD; Lori D. Prok, MD. Published Online: February 26, 2014. doi:10.1001/jamadermatol.2013.8358. Conflict of Interest Disclosures: None reported. REFERENCES 1. Baran R, Kint A. Onychomatrixoma: filamentous tufted tumour in the matrix of a funnel-shaped nail: a new entity (report of three cases). Br J Dermatol. 1992;126(5):510-515.
450
crine syringofibroadenoma, onycholemmal horn, subungual exostoses, subungual osteochondroma, and malignant proliferating onycholemmal cyst.4,6 It has been suggested that the melanonychia is due to the activation of matrical melanocytes as opposed to melanocyte hyperplasia.5,7 This is consistent with our findings, which showed a normal melanocyte density, defined as 8 to 17 melanocytes per millimeter of sectioned matrical epithelium.8 We believe that the clinical appearance was due to lentiginous pigment along the basal layers of the epidermis, which may have been induced by dermal fibroblasts in a process akin to epidermal pigmentation in dermatofibromas. The latter are known to demonstrate hyperpigmentation of the overlying epidermis induced by cytokine expression of dermal fibroblasts.9 Similarly, we propose that the fibrous stroma of onychomatricomas is capable of stimulating melanogenesis. Histologically, OMs are benign, biphasic fibroepithelial tumors of nail matrix origin. Tumors can have broad bases with filiform projections, sometimes extending into the lateral horn. Histopathologic features include epithelial projections of squamoid cells with keratotic zones overlying a fibrous stroma populated by spindled cells. Though recently, Perrin and colleagues3 described a broader histologic spectrum. Overlying nail plates contain transversely arranged lacunae filled with serous fluid, frequently described as “wormwood-like cavities.”10 Uniquely, OM can produce nail plate substances, as opposed to other lesions that secondarily distort the nail plate. Sending the nail plate with the tumor for histologic examination can assist with the diagnosis.3,6 The treatment of choice is complete surgical excision with histologic examination of the specimen. Some recommend including a safety margin of normal nail matrix during excision to safeguard against recurrence.2 There have been no reports of recurrence after complete surgical intervention.6,8
2. Gaertner EM, Gordon M, Reed T. Onychomatricoma: case report of an unusual subungual tumor with literature review. J Cutan Pathol. 2009;36(suppl 1):66-69.
7. Perrin C. Tumors of the nail unit: a review, part I: acquired localized longitudinal melanonychia and erythronychia. Am J Dermatopathol. 2013;35(6):621-636.
3. Perrin C, Baran R, Balaguer T, et al. Onychomatricoma: new clinical and histological features: a review of 19 tumors. Am J Dermatopathol. 2010;32(1):1-8.
8. Ko CJ, Shi L, Barr RJ, Mölne L, Ternesten-Bratel A, Headington JT. Unguioblastoma and unguioblastic fibroma—an expanded spectrum of onychomatricoma. J Cutan Pathol. 2004;31(4):307-311.
4. Cañueto J, Santos-Briz A, García JL, Robledo C, Unamuno P. Onychomatricoma: genome-wide analyses of a rare nail matrix tumor. J Am Acad Dermatol. 2011;64(3):573-578. 5. Fayol J, Baran R, Perrin C, Labrousse F. Onychomatricoma with misleading features. Acta Derm Venereol. 2000;80(5):370-372.
9. Shishido E, Kadono S, Manaka I, Kawashima M, Imokawa G. The mechanism of epidermal hyperpigmentation in dermatofibroma is associated with stem cell factor and hepatocyte growth factor expression. J Invest Dermatol. 2001;117(3):627-633.
6. Goutos I, Furniss D, Smith GD. Onychomatricoma: an unusual case of ungual pathology: case report and review of the literature. J Plast Reconstr Aesthet Surg. 2010;63(1):e54-e57.
10. Perrin C, Goettmann S, Baran R. Onychomatricoma: clinical and histopathologic findings in 12 cases. J Am Acad Dermatol. 1998;39(4, pt 1):560-564.
JAMA Dermatology April 2014 Volume 150, Number 4
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://archderm.jamanetwork.com/ by a Karolinska Institutet University Library User on 05/22/2015
jamadermatology.com
JAMA Dermatology Clinicopathological Challenge
Longitudinal Melanonychia of the Toenail Charlene Lam, MD, MPH; Grace W. Weyant, MD; Elizabeth M. Billingsley, MD
A man in his 60s presented with a pigmented nail streak on the left fourth toenail that had been present for 10 months. He denied pain, tenderness, or trauma. Physical examination revealed a 4-mm wide pigmented streak with varying shades of brown and longitudinal ridging (Figure, A). The nail fold was unin-
A
volved. Because of suspicion for melanoma, a biopsy was recommended. A nail avulsion was performed and demonstrated a 3-mm tan papule beneath the proximal nail fold (Figure, B). The histologic findings are shown in Figure, C. What is your diagnosis?
B
C
Figure. A, Photograph of the left fourth toenail. B, Photograph of the left fourth toenail after nail avulsion. C, Histologic analysis of the tumor (hematoxylin-eosin, original magnification ×10).
jamadermatology.com
JAMA Dermatology April 2014 Volume 150, Number 4
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://archderm.jamanetwork.com/ by a Karolinska Institutet University Library User on 05/22/2015
449
Clinical Review & Education JAMA Dermatology Clinicopathological Challenge
Diagnosis Onychomatricoma (OM)
Microscopic Findings and Clinical Course The tumor was composed of papillomatous epithelium overlying stroma occupied by a collection of cytologically banal spindled cells that expressed CD34 but not epithelial membrane antigen, glucose transporter protein 1, factor XIIIa, S100, and melan-A (Figure, C). Melanocytes were normal in number and distribution as determined by hematoxylin-eosin stain and immunostaining with S100 and melan-A. The tumor was completely excised, and there have been no signs of recurrence for at least 6 months.
Discussion Onychomatricomas were first described by Baran and Kint1 in 1992. They are rare, slow-growing, painless tumors of the nail matrix. Onychomatricoma tends to appear in middle-aged to older individuals, with a possible female predilection.2,3 Fingers are more commonly affected than toes. The etiology of OM is not known, though trauma and onychomycosis have been proposed as associated factors.4,5 A recent genomic analysis of OM demonstrated genomic losses in the tumors.4 The classic clinical presentation involves 4 components: (1) yellow, thickened longitudinal band with prominent ridging on the nail plate; (2) increased transverse overcurvature of the nail; (3) splinter hemorrhages proximally; and (4) a matrical tumor evident after nail avulsion.6 However, there are atypical presentations including melanoncyhia,5 cutaneous horn,2 pterygium, nail bed bleeding, and onychomycosis.2,4 The differential diagnosis includes acquired fibrokeratoma, periungual fibroma, subungual verruca vulgaris, Bowen disease, squamous cell carcinoma, melanoma, fibroepithelioma of Pinkus, ecARTICLE INFORMATION Author Affiliations: Penn State Milton S. Hershey Medical Center, Hershey, Pennsylvania. Corresponding Author: Elizabeth M. Billingsley, MD, Penn State Milton S. Hershey Medical Center, 500 University Dr, Mail Code HU14, Hershey, PA 17033 ([email protected]). Section Editor: Molly A. Hinshaw, MD; Assistant Section Editors: Soon Bahrami, MD; Nicole Fett, MD, MSCE; Anna K. Haemel, MD; Arni K. Kristjansson, MD; Lori D. Prok, MD. Published Online: February 26, 2014. doi:10.1001/jamadermatol.2013.8358. Conflict of Interest Disclosures: None reported. REFERENCES 1. Baran R, Kint A. Onychomatrixoma: filamentous tufted tumour in the matrix of a funnel-shaped nail: a new entity (report of three cases). Br J Dermatol. 1992;126(5):510-515.
450
crine syringofibroadenoma, onycholemmal horn, subungual exostoses, subungual osteochondroma, and malignant proliferating onycholemmal cyst.4,6 It has been suggested that the melanonychia is due to the activation of matrical melanocytes as opposed to melanocyte hyperplasia.5,7 This is consistent with our findings, which showed a normal melanocyte density, defined as 8 to 17 melanocytes per millimeter of sectioned matrical epithelium.8 We believe that the clinical appearance was due to lentiginous pigment along the basal layers of the epidermis, which may have been induced by dermal fibroblasts in a process akin to epidermal pigmentation in dermatofibromas. The latter are known to demonstrate hyperpigmentation of the overlying epidermis induced by cytokine expression of dermal fibroblasts.9 Similarly, we propose that the fibrous stroma of onychomatricomas is capable of stimulating melanogenesis. Histologically, OMs are benign, biphasic fibroepithelial tumors of nail matrix origin. Tumors can have broad bases with filiform projections, sometimes extending into the lateral horn. Histopathologic features include epithelial projections of squamoid cells with keratotic zones overlying a fibrous stroma populated by spindled cells. Though recently, Perrin and colleagues3 described a broader histologic spectrum. Overlying nail plates contain transversely arranged lacunae filled with serous fluid, frequently described as “wormwood-like cavities.”10 Uniquely, OM can produce nail plate substances, as opposed to other lesions that secondarily distort the nail plate. Sending the nail plate with the tumor for histologic examination can assist with the diagnosis.3,6 The treatment of choice is complete surgical excision with histologic examination of the specimen. Some recommend including a safety margin of normal nail matrix during excision to safeguard against recurrence.2 There have been no reports of recurrence after complete surgical intervention.6,8
2. Gaertner EM, Gordon M, Reed T. Onychomatricoma: case report of an unusual subungual tumor with literature review. J Cutan Pathol. 2009;36(suppl 1):66-69.
7. Perrin C. Tumors of the nail unit: a review, part I: acquired localized longitudinal melanonychia and erythronychia. Am J Dermatopathol. 2013;35(6):621-636.
3. Perrin C, Baran R, Balaguer T, et al. Onychomatricoma: new clinical and histological features: a review of 19 tumors. Am J Dermatopathol. 2010;32(1):1-8.
8. Ko CJ, Shi L, Barr RJ, Mölne L, Ternesten-Bratel A, Headington JT. Unguioblastoma and unguioblastic fibroma—an expanded spectrum of onychomatricoma. J Cutan Pathol. 2004;31(4):307-311.
4. Cañueto J, Santos-Briz A, García JL, Robledo C, Unamuno P. Onychomatricoma: genome-wide analyses of a rare nail matrix tumor. J Am Acad Dermatol. 2011;64(3):573-578. 5. Fayol J, Baran R, Perrin C, Labrousse F. Onychomatricoma with misleading features. Acta Derm Venereol. 2000;80(5):370-372.
9. Shishido E, Kadono S, Manaka I, Kawashima M, Imokawa G. The mechanism of epidermal hyperpigmentation in dermatofibroma is associated with stem cell factor and hepatocyte growth factor expression. J Invest Dermatol. 2001;117(3):627-633.
6. Goutos I, Furniss D, Smith GD. Onychomatricoma: an unusual case of ungual pathology: case report and review of the literature. J Plast Reconstr Aesthet Surg. 2010;63(1):e54-e57.
10. Perrin C, Goettmann S, Baran R. Onychomatricoma: clinical and histopathologic findings in 12 cases. J Am Acad Dermatol. 1998;39(4, pt 1):560-564.
JAMA Dermatology April 2014 Volume 150, Number 4
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://archderm.jamanetwork.com/ by a Karolinska Institutet University Library User on 05/22/2015
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