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Napa Valley Dermatopathology 2018

Nail pathology II: Non-melanocytic Neoplasms

Beth S. Ruben, MDDirector, Dermatopathology

Palo Alto Medical Foundation, Palo Alto, CA

Professor of Dermatology

University of California, San Francisco

Epithelial and other neoplasms

of the nail unit

• Some are counterparts to those found

elsewhere

• Some are entities unique to this site

• Unusual features can create diagnostic

quandaries

• Diagnosis often depends on the adequacy of the

specimen and the clinical history

Epithelial and other neoplasms

• Benign

– Onychopapilloma

– Subungual epidermoid

inclusions

– Onychomatricoma

– Onychocytic matricoma

– Superficial acral

fibromyxoma

• Malignant

– SCCIS/SCC

– Keratoacanthoma

– Subungual tumors of

incontinentia pigmenti

– Onycholemmal CA

– Onychocytic CA (?)

– Papillary adenoCA

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Tosti A, Schneider SL, Ramirez-Quizon MN, Zaiac M, Miteva M.

Clinical, dermoscopic, and pathologic features of onychopapilloma: A

review of 47 cases. Journal of the American Academy of Dermatology.

2016;74(3):521-526.

Onychopapilloma

• Clinical findings

– Erythronychia

– Splinter hemorrhage

– Melanonychia

– Leukonychia

– Distal hyperkeratosis

– Distal splitting

Courtesy of Tara Miller, MD

Histologic features

• Hyperplasia of distal matrix and nail bed epithelium,

papillated distally

• Distal subungual hyperkeratosis/parakeratosis

• Hemorrhage

• Matrical metaplasia (eosinophilic, anucleated cell layer in

nail bed)

• Large and multinucleate distal nail bed keratinocytes

• Sometimes pigmentation (melanocytic activation)

• Often need intact lesion to make definitive diagnosis

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Courtesy of Leslie Robinson-Bostom, MD

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Baran R, Perrin C. Longitudinal erythronychia with distal

subungual keratosis: onychopapilloma of the nail bed and

Bowen’s disease. Br J Dermatol. 2000;143(1):132-135.

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Courtesy, of Jon Starr, MD

Verruca vulgaris

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Subungual epidermoid inclusions

• Small aggregates of keratinocytes or cysts that can be found under the epithelium of the nail bed

• An incidental finding, or associated with nail dystrophy, especially a shortened and dystrophic nail plate, or clubbing

• A history of trauma is common, and there may be associated underlying bony abnormalities as well

• There may be associated hyperkeratosis of the nail bed• Less cystic variants can be mistaken for squamous cell

carcinoma or other neoplasms

Lewin K. Br J Dermatol 77:241, 1965

Lewin K. Br J Dermatol 81(671),1969

Fanti PA, Tosti A. Dermatologica 178(4):209-12, 1989

Bukhari IA, Al-Mugharbel R. Saudi Med J Apr;25(4):522-3, 2004Telang GH and Jellinek N. J Am Acad Dermatol 56:336-9, 2007

Ruben BS, LeBoit PE. J Cutan Pathol. 2008 Jan;35(1):97.

Collection of Monica Lawry, M.D.

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OnychomatricomaBaran and Kint

Onychomatricoma

Clinical presentation

Thickened nail plate Transverse overcurvature

Splinter

hemorrhages

Nodule

Courtesy of Monica Lawry, MD

Hollow area within tumor

Nail bed

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Specimen for pathology

Onychomatricoma

Clinical features:• Mean age 50.5 (24-68), lighter-skinned patients• Fingers most often affected, esp. thumb and index• Female to male 2.16:1• Thickened yellowish nail, transverse overcurvature, splinter

hemorrhages, sometimes pigmented• Nodular area corresponding to the matrix• Rarely recurs after surgery

Perrin C, Baran R, Balaguer T, et al. Am J Dermatopathol. 2010;32(1):1-8.

Di Chiacchio N, Tavares GT, Tosti A, et al. Br J Dermatol. 2015;173(5):1305-1307.

Reserva JL, Ruben BS, Venna SS. Skin Appendage Disord. 2017;3(1):32-35.

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OnychomatricomaKey histologic features: • Multiple fibroepithelial projections• Thick V-shaped keratogenous zone, mimics normal matrix• Matrical hyperplasia of varying degree• “Glove-finger” appearance of nail plate and matrix interaction• Altered nail plate thin proximally, thick distally, with multiple

cavities (wormwood)• Fibrocellular stroma of varying degree

– CD34+; CD99, S100, EMA-– More cellular superficially, perpendicular collagen bundles deeply– Myxoid stroma similar to superficial acral fibromyxoma, rare

Normal nail

Fibroepithelial

component

Thick, altered nail plate

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Courtesy of A. Christine Miller, MD

Pigmented onychomatricoma

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Pleomorphic OM

Courtesy of Laura Pincus, MD

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“Pleomorphic” OM

• Only seven cases now reported:

– 2 as “unguioblastic fibroma”

– 2 possibly as pleomorphic fibroma

– 2 in a large series of 19 cases of OM

• Although pleomorphic, no history of adverse biologic behavior

Fernandez-Flores’ A, Barja-Lopez J-M. J. Cutan. Pathol. 2014;41(7):555-560.

Petersson F, Tang ALY, Jin ACE, Barr RJ, Lee VK. Am J Dermatopathol 2010;32(4):387-391.

Ki-67

Nail clipping for diagnosis

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Miteva M. et al. Arch Dermatol.

2011;147(9):1117–1118.

Tallon B, Strydom F, Emanuel PO.

J Cutan Pathol. 2013;40(1):2–3.

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.

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OnychomatricomaDifferential Diagnosis- Histologic

• Angiofibroma (Koenen’s tumor)• Acquired digital fibrokeratoma• Cellular digital fibroma• Perineurioma• Pleomorphic fibroma• Superficial acral fibromyxoma• Verruca vulgaris• SCC in situ (rarely)

CD34+

EMA

S100

CD99

Superficial acral fibromyxoma

Courtesy of Brad Naylor, DPM

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CD34

EMA

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Fetsch JF, Laskin WB,

Miettinen M. Hum Pathol.

2001 Jul;32(7):704-14.

Superficial acral fibromyxomaClinical features

• A benign spindle cell proliferation• Predilection for hands and feet, fingers and toes,

often with close relationship to nail unit• Broad age range (mean, 43)• Duration 3 mos to 30 years• Size 0.6 cm-5 cm, may impinge on bone• Behavior: most did not recur after excision

Fetsch JF, Laskin WB, Miettinen M. Hum Pathol. 2001 Jul;32(7):704-14.

Superficial acral fibromyxomaHistologic features

• Spindled to stellate cells • Random, loose storiform or fascicular patterns• Myxoid to collagenous, prominent mast cells• Occasional multinucleate cells, rare mitoses• CD34+, CD99 variable +, EMA focal/–• Nestin positive, RB1 loss• Probable fibroblastic differentiation

Fetsch JF, Laskin WB, Miettinen M. Hum Pathol. 2001 Jul;32(7):704-14.

Cullen D, Díaz Recuero JL, Cullen R et all. Am J Dermatopathol. 2017;39(1):14-22.

Agaimy A, Michal M, Giedl J et al. Hum Pathol. 2017;60:192-198.

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Chattopadhyay M, Farrant P, Higgins E, Hay R, Calonje E. Clin Exp Dermatol. 2010 Oct;35(7):807-9

Courtesy of Jeff North, MD

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Pleomorphic fibroma

Angiofibroma

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Perrin C, Cannata GE, Bossard C, et al. Onychocytic matricoma

presenting as pachymelanonychia longitudinal. A new entity (report of

five cases). Am J Dermatopathol. 2012;34(1):54–59.

Courtesy of Mark Holzberg, MD

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Melan-A

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Perrin C, Cannata GE, Bossard C, et al. Onychocytic matricoma presenting as

pachymelanonychia longitudinal. A new entity (report of five cases). Am J

Dermatopathol. 2012;34(1):54–59.

Acanthotic type

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Papillomatous Keratogenous

Melanocytes and melanin

Bon-Mardion M, Poulalhon N, Balme B, Thomas L. Ungual

seborrheic keratosis. J Eur Acad Dermatol Venereol.

2010;24(9):1102–1104.

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Wanat KA, Reid E, Rubin AI. Onychocytic matricoma: a new, important nail-unit

tumor mistaken for a foreign body. JAMA Dermatol. 2014;150(3):335-337.

Stinco G, Errichetti E, Patrone P. Ungual seborrhoeic keratosis: report of a case

and its dermoscopic features. J Eur Acad Dermatol Venereol. 2014.

doi:10.1111/jdv.12866.

Nail dystrophy began 3 years ago, slowly more raised

Courtesy of Drs. Jane Bellet and Ken Ellington

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proximal

distal

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SCC of the nail unit

• Most common tumor of nail unit, but still

uncommon

• Atypical clinical presentations the rule– Dystrophy, onycholysis, ulceration, paronychia, nail loss, and

rarely longitudinal melanonychia

• Predisposing factors– Immunosuppression

– Oncogenic HPV

– Radiodermatitis

Squamous cell carcinomaIn situ Invasive

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Partial nail plate avulsion reveals nail bed abnormality

Sneaky SCC

Courtesy of Monica Lawry, MD

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SCCIS of the nail unit

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Pigmented SCCIS

Subungual keratoacanthoma

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von Kossa

Painful subungual tumorsof incontinentia pigmenti

• Well-recognized but rare complication of IP, a late manifestation

• Corresponds to the verrucous stage, IP

• Fingers > toes

• DDX: subungual keratoacanthoma, verruca, epidermoid cysts, subungual fibroma, chronic paronychia

• Intense pain and osteolysis may occur

• Excision or amputation may be necessary

• Retinoids have been used with some promise

Young et al. JAAD 2005

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Chaser BE, Renszel KM, Crowson AN, et al. Onycholemmal carcinoma: A morphologic comparison of 6 reported cases. J. Am. Acad. Dermatol. 2013;68(2):290–295.

• Clinical features:

– Female to male 1:1

– Middle age to older patients

– Finger: thumb: toe: unknown 3:1:1:1

– Symptoms/signs: ulceration, swelling, paronychia-like, onycholysis, periungual erythema, pain

– May abut the bone but no bony involvement

– Indolent course (no aggressive behavior)

– Treatment: Mohs surgery, excision, nail unit excision, radiation, amputation

– Conservative treatment advocated

Chaser BE, Renszel KM, Crowson AN, et al. Onycholemmal carcinoma: A morphologic

comparison of 6 reported cases. J. Am. Acad. Dermatol. 2013;68(2):290–295.

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• Histologic features

– Cytologically bland

– Poorly circumscribed, infiltrative pattern

– Lobular and cystic

– Abrupt keratinization (reminiscent of proliferating pilar

tumor)

– Authors consider this an acral SCC

– 1 case studied was negative for HPV

Chaser BE, Renszel KM, Crowson AN, et al. Onycholemmal carcinoma: A morphologic

comparison of 6 reported cases. J. Am. Acad. Dermatol. 2013;68(2):290–295.

Courtesy of Michael Morgan, MD

Onycholemmal carcinoma

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Perrin C, Langbein L, Ambrossetti D, Erfan N, Schweizer J, Michiels J-F. Onychocytic carcinoma: a new

entity. Am J Dermatopathol. 2013;35(6):679-684.

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Perrin C, Langbein L, Ambrossetti D, Erfan N, Schweizer J, Michiels J-F. Onychocytic carcinoma: a new

entity. Am J Dermatopathol. 2013;35(6):679-684.

Wang L, Gao T, Wang G. Invasive onychocytic carcinoma. J Cutan Pathol. 2015

May;42(5):361-7

• 51 yo woman, ulceration of left ring finger, 4 years

• Began with trauma, then formed a longitudinal split

• Gradual destruction of whole nail bed

• First biopsy inconclusive

Wang L, Gao T, Wang G. Invasive onychocytic carcinoma. J Cutan Pathol 2015 May;42(5):361-7.

Invasive

Matrix-like

cytology

Keratinization

Retiform

contour

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Jih DM, Elenitsas R, Vittorio CC, Berkowitz AR, Seykora JT. Aggressive

digital papillary adenocarcinoma: a case report and review of the literature.

Am J Dermatopathol. 2001;23(2):154-157.

Digital papillary adenocarcinomaHistory

• First described by Helwig, 1979 (AAD CPC)

• Rare low grade malignant adnexal tumor

• Formerly, aggressive digital papillary adenoma (ADPA)

• Despite somewhat bland histologic appearance, some cases found

to behave aggressively

• 2000, Duke et al propose ADPA is malignant without a benign

counterpart, renaming as PDA to reflect this behavior, suggest

aggressive treatment

• 2009, Hsu et al suggest that wide excision may be adequate for

some more limited cases (use Ki-67 proliferation index as a guide)

Digital papillary adenocarcinomaClinical features

• Painful or painless cystic mass, acral skin, volar surfaces of fingers and toes

• Male predominance

• Unusual presentations include as PG, hemangioma, SCC-like, osteomyelitis, soft tissue infection, and paronychia

• Preferred location: between nail unit and DIP

Kao GF, Helwig EB, Graham JH. J Cutan Pathol. 1987 Jun;14(3):129-46. Duke WH, Sherrod TT, Lupton GP. Am J Surg Pathol. 2000 Jun;24(6):775-84.

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Courtesy of Tara Miller, MD

Digital papillary adenocarcinomaHistology

Mixed papillary, tubuloalveolar, solid, cystic patterns;

variable atypia, mitotic rate, necrosis

Squamous metaplasia, clear cells, spindle cells

Stains with S100, CEA, p63

Also EMA, ER, PR, CK7, CK77, PHLDA, SMA, AR

May contain myoepithelial cells

No histologic features predict biologic behavior

Ki-67 proliferation rate?Suchak R et al. Am J Surg Path.36:1883-91, 2012

Weingertner N et al. J Am Acad Dermatol. 2017;77(3):549-558.e1.

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Digital papillary adenocarcinomaDifferential diagnosis

• Metastatic carcinoma

• Tubular apocrine adenoma

• Hidradenoma

Digital papillary adenocarcinomaPrognosis and treatment

• Local recurrence in 5%, up to 50% if not widely

excised

• Metastasis 12-14%, often to lung (70%)

• In some series, metastatic rate approaches 50%

• Treatment: wide local excision, amputation,

Mohs surgery, sentinel node sampling??

Morita R et al. Plast Reconstr Surg. 2006 Feb;117(2):710-2.Rismiller K, Knackstedt TJ Dermatol Surg. March 2018.

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Take home points

• Epithelial and other neoplasms may have

distinctive features in the nail unit

• Orientation of the tissue may be key to recognition

• Determining benign versus malignant can

sometimes be tricky

• Some diagnoses are unique to this site

• Be on the lookout for new entities!