Clinical Review & Education

JAMA Clinical Challenge

Ulcerated Nodule of the Fingernail

Shari R. Lipner, MD, PhD

Figure 1. Left, Physical examination of left second fingernail. Right, Histopathologic findings under low-power
magnification (hematoxylin-eosin, original magnification ×20).

A woman in her 60s presented with a 2-year history of an abnormal left second fingernail.
A previous biopsy showed a pyogenic granuloma, and she had been treated with curettage and WHAT WOULD YOU DO NEXT?
electrodessication. In the few months before presentation, she experienced partial nail loss
and her nail had become painful with intermittent drainage. Her medical history was significant A. Treat with cryotherapy
for streptococcal glomerulonephritis and 2 prior kidney transplants. Her medications included
prednisone, tacrolimus, and mycophenolate mofetil. Physical examination of the left second
B. Perform immunohistochemical
fingernail showed a tender ulcerated nodule encompassing the nail bed with near-complete
analysis on the biopsy specimen
nail loss and purulent drainage (Figure 1, left). A nail biopsy was repeated by performing a 4-mm
punch through the nail bed. The specimen was analyzed by histopathology with hematoxylin-
eosin staining and once again showed a pyogenic granuloma–like response characterized by C. Perform tissue culture for bacterial
proliferating blood vessels in a background of fibrosis and reactive plasmacytic infiltration and fungal organisms
(Figure1,right).Carefulinspectionofthepyogenicgranulomatousprocessathigherpowerdem-
onstrated atypical epithelioid and spindled cells adjacent to blood vessels. D. Provide reassurance

Diagnosis a patient evaluated for healing after a surgical procedure (electrodes-

Subungual amelanotic melanoma sication and curettage for pyogenic granuloma).

What to Do Next Discussion

B. Perform immunohistochemical analysis on the biopsy specimen
The keys to the correct diagnosis are the history of progressive
nail loss and pain, the physical examination findings of an ulcerated
nodule with near-complete nail loss, and the biopsy results. Under low-
power magnification, the biopsy specimen resembles a pyogenic
granuloma, but clues to malignancy are the atypical epitheliotropic
and dermal spindled and epithelioid cells. Immunohistochemistry with
Melan-A highlights these cells, which are diagnostic of subungual acral
lentiginous melanoma (Figure 2),1 at a Breslow depth of 1.18 mm.
Cryotherapy (liquid nitrogen treatment) is a reasonable treatment for
a pyogenic granuloma or a verruca (wart). Tissue culture is an appro-
priate technique when a diagnosis of bacterial, atypical bacterial,
or deep fungal infection is considered. Reassurance is suitable for
Subungual melanoma is a type of acral lentiginous melanoma that
arises in the nail unit. It accounts for only 2% of all melanomas in
white patients but for 17% in Hong-Kong Chinese patients, 23% in
Japanese patients, and up to 25% in African patients.2 Subungual
amelanotic melanoma, which lacks pigment, is difficult to diagnose
both clinically and pathologically.1,3 Misdiagnosis has been re-
ported in more than 50% of cases, with the majority of patients un-
dergoing an inappropriate invasive procedure before the correct di-
agnosis is made.4 On physical examination, subungual amelanotic
melanoma may mimic other conditions, including pyogenic granu-
loma, verruca, and squamous cell carcinoma. Although amelanotic
tumors account for only 10% of all melanomas, they represent up
to 30% of nail melanomas.5,6

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 Clinical Review & Education JAMA Clinical Challenge

elliptical excision that extends down to the periosteum. Patho-

Figure 2. Immunohistochemistry with Melan-A stain, which detects Melan-A
protein antigen on the surface of melanocytes (diaminobenzidine
detection system with brown chromogen and blue counterstain, original
magnification ×200).
Subungual melanoma has 2 typical clinical presentations.
Longitudinal melanonychia, defined as a brown-black band of the
nail plate, is the presenting sign in more than two-thirds of subun-
gual melanoma cases.7 In the less common presentation (subungual
amelanotic melanoma), there is often a history of trauma with an ul-
cerating or vascular nodule involving the thumb or hallux, with vary-
ing degrees of intact nail plate. Dermoscopy may show features sug-
gesting subungual amelanotic melanoma but cannot be used to
distinguish between amelanotic melanoma, squamous cell carci-
noma, and pyogenic granuloma.6 A typical dermoscopic finding is
a red background with a milky-red veil and irregular vessels centrally
and crusts at the periphery.
The standard means of diagnosing amelanotic melanoma is
a nail biopsy. The nail bed can be sampled using a punch or by an
logically, subungual amelanotic melanomas may resemble
pyogenic granulomas and sarcomas. Immunochemistry, using
melanocytic markers such as S100 protein, HMB–45, and Melan-A
are used to differentiate amelanotic melanoma from other
malignancies.1
Nail melanomas are typically diagnosed in late stages
and therefore are associated with poorer prognoses than similarly
staged cutaneous melanomas, with 5-year survival rates of
10% to 30%. 2,8 Breslow thickness is an important indicator
of prognosis and metastasis for subungual melanoma, as in other
melanoma subtypes. Other important factors are Clark level
(histologic level of invasion), ulceration, amelanosis, lymphocyte
infiltration, and mitotic rate. The most common site of metastasis
is regional lymph nodes.9 Subungual melanoma in situ can be
treated with an en-bloc excision with no difference in survival
compared with digital amputation. Amputation is routinely per-
formed for invasive tumors. 5 Sentinel lymph node biopsy is
recommended for tumors thicker than 1 mm. In the setting of
metastatic disease, lymph node dissection is performed and che-
motherapy may be indicated.
Early diagnosis and prompt treatment may significantly alter
prognosis. Therefore, any nonhealing nail nodule should prompt
a nail biopsy to rule out amelanotic melanoma, even when prior his-
topathology results were benign.
Patient Outcome
The patient underwent distal interphalangeal disarticulation and sen-
tinel lymph node mapping and biopsy, which did not identify meta-
static disease. After surgery, she had good range of motion of her
second digit and was able to perform activities of daily living.

ARTICLE INFORMATION
Author Affiliation: Department of Dermatology,
Weill Cornell Medicine, New York, New York.
Corresponding Author: Shari Lipner, MD, PhD,
Department of Dermatology, Weill Cornell
Medicine, 1305 York Ave, 9th Floor, New York,
New York 10021 (SHL9032@med.cornell.edu).
Section Editor: Mary McGrae McDermott, MD,
Senior Editor.
Published Online: February 16, 2018.
doi:10.1001/jama.2018.0179
Conflict of Interest Disclosures: The author has
completed and submitted the ICMJE Form for
Disclosure of Potential Conflicts of Interest and
none were reported.
Meeting Presentation: This article was presented
at the American Academy of Dermatology
2018 Annual Meeting; February 16, 2018;
San Diego, California.
Additional Contributions: I thank Cynthia Magro,
MD (Department of Pathology, Weill Cornell
Medicine), for her help with the pathology and
figure legends and thank the patient for providing
permission to share her information. Dr Magro
received no compensation for her contributions.
Submissions: We encourage authors to submit
papers for consideration as a JAMA Clinical
Challenge. Please contact Dr McDermott at
mdm608@northwestern.edu.
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