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VOLUME 67, NUMBER 2

Department of Dermatology, University Hospital,

Ghenta; Department of Medical Oncology, OLV
van Lourdes Hospital, Waregemb; Departments of
Medical Oncologyc and Dermatology,d AZ Groeninge Hospital, Kortrijk; Dr Suys also has a
private practice in Kortrijk, Belgium
Funding sources: None.
Fig 2. Extensive locoregional progression.

effects on different cell types.2 Tocilizumab has been

used for rheumatoid arthritis, systemic onset juvenile
idiopathic arthritis, Castleman disease, and Crohns
disease.1
Several studies have reported that tocilizumab
therapy is generally well tolerated. Adverse reactions
are quite common, up to 90%, but these are mostly
low-grade reactions. The most common adverse
events are infections and infestations (mostly upper
respiratory tract infections), gastrointestinal disorders
(nausea, vomiting, diarrhea, perforation), infusion
reactions and hypersensitivity reactions, hematological abnormalities, altered lipid profile, and liver
function disorders. All these adverse events seem to
be equally prevalent with tocilizumab therapy as with
classic disease modifying antirheumatic drugs as
methotrexate.3 Regarding the risk of malignancy,
one could suppose that the immunosuppressive
properties of tocilizumab may be a concern.
However, the available data do not show an increased
malignancy risk with tocilizumab compared with
placebo or disease-modifying antirheumatic drugs.2,3
With regard to malignant melanoma, IL-6 has
been found to be a potent inhibitor of melanoma
cell adhesion and proliferation. Treatment with the
IL-6/sIL-6R complex showed growth inhibition of
melanoma cells.4 Thus, it could be hypothesized that
blocking the IL-6 signal can result in uncontrolled
growth of melanoma, as occurred in our patient. It
could be argued whether the melanoma was already
present before tocilizumab was started. IL-6 is particularly important in inhibiting growth of early-stage
melanoma.5 Blocking IL-6 could lead to rapid progression of melanoma.
This case focuses attention on the mid- to longterm side effects of the relatively new class of
biological treatments. Postmarketing surveillance
is an important tool to learn about long-term side
effects. This case also emphasizes the importance
of a dermatological check-up before starting those
medications.
Michiel Bonny, MD,a Veronique Buyse, MD,b,c and
Erwin Suys, MDd

Conflicts of interest: None declared.

Correspondence to: Michiel Bonny, MD, De Pintelaan 185, 9000 Ghent, Belgium
E-mail: michiel.bonny@ugent.be
REFERENCES
1. Venkiteshwaran A. Tocilizumab. MAbs 2009;1:432-8.
2. Bannwarth B, Richez C. Clinical safety of tocilizumab in rheumatoid arthtritis. Expert Opin Drug Saf 2011;10:123-31.
3. Patel A, Moreland L. Interleukin-6 inhibition for treatment of
theumatoid arthritis: A review of tocilizumab therapy. Drug Des
Devel Ther 2010;4:263-78.
4. Wagley Y, Yoo Y-C, Seo HG, Rhee MH, Kim TH, Kang KW, et al.
The IL-6/sIL-6R treatment of a malignant melanoma cell line
enhances susceptibility to TNF-a-induced apoptosis. Biochem
Biophys Res Commun 2007;354:985-91.
5. Lu C, Vickers M, Kerbel R. Interleukin 6: A fibroblast-derived
growth inhibitor of human melanoma cells from early but not
advanced stages of tumor progression. Proc Natl Acad Sci U S A
1992;89:9215-9.
http://dx.doi.org/10.1016/j.jaad.2011.08.033

Cutaneous metastasis of thyroid carcinoma

mimicking Mondor disease
To the Editor: Mondor disease, typified by superficial
thrombophlebitis, has been previously reported in
association with breast carcinoma1,2 and metastatic
lung cancer.3 We report a case of biopsy-confirmed
cutaneous metastasis of insular thyroid carcinoma
mimicking Mondor disease.
A 77-year-old woman, with a history of recurrent
insular thyroid carcinoma treated with radioactive
iodine, radiation, and multiple resections, presented
with a progressively enlarging right-sided neck mass
that was later found to be recurrent thyroid carcinoma and a plaque on the superior lateral left breast,
which prompted dermatologic evaluation. The patient reported a history of chronic left arm and breast
lymphedema of unknown etiology. The lesion on
the left breast developed 2 months prior to this
hospital admission and was intermittently painful. A
breast biopsy had been performed 6 months earlier,
adjacent to the lesion, which showed the lesion to be
benign; therefore the patient was given a clinical
diagnosis of Mondor disease and was advised that
the superficial thrombophlebitis may have resulted
as a complication of the biopsy procedure. Warm

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Fig 1. Cutaneous metastasis of insular thyroid carcinoma

mimicking Mondor disease. Image shows an indurated,
bound-down plaque with prominent vessels located on
left superolateral breast.

compresses did not alleviate pain, and the skin lesion

became progressively harder, larger, and more
bound down. Subsequent mammography showed
diffuse skin thickening, suspected to be inflammatory breast cancer.
Physical examination of the left lateral superior
breast revealed an 8- 3 16-cm firmly indurated,
bound-down plaque with prominent vessels (Fig 1).
The clinical differential diagnosis included: Mondor
disease, morphea, lipodermatosclerosis resulting
from chronic edema, breast carcinoma, and cutaneous metastasis. Lymphedema of the left upper extremity and left axillary lymphadenopathy were also
noted.
A skin biopsy specimen revealed nests and
cords of strikingly atypical epithelial cells arrayed
throughout a sclerotic reticular dermis (Fig 2). The
constituent cells demonstrated marked nuclear pleomorphism and nucleomegaly. Immunoperoxidase
staining analysis of the specimen demonstrated
CK7 and thyroid transcription factor (TTF-1) expression with an absence of CK20 labeling. There
was no evidence of estrogen receptor and progesterone receptor expression. D2-40 immunostaining
did not reveal lymphatic vascular invasion. A diagnosis of metastatic insular thyroid carcinoma was
rendered.
Mondor disease represents superficial thrombophlebitis affecting the anterolateral thoracoabdominal wall; a similar superficial thrombophlebitis
affecting the penis has also been described.2,4
Reported associations include trauma, surgical procedure on breast (biopsy, augmentation, or reduction), sentinel lymph node biopsy, mastitis/breast

AUGUST 2012

Fig 2. Insular thyroid carcinoma. Punch biopsy specimen

shows diffuse sclerosis of reticular dermis, and entrapped
collections of epithelial cells are apparent. At higher
magnification (inset), marked nuclear atypicality and pleomorphism are appreciable, but specific differentiation is
not discernible. (Hematoxylin-eosin stain.)

abscess, pendulous breasts, breast carcinoma (invasive ductal carcinoma, invasive lobular carcinoma),
lung carcinoma (small cell carcinoma), and hypercoagulable states.2 In cases of associated malignancy, it is believed that Mondor disease results
from hypercoagulability and is a self-limited condition. Herein we report a case of cutaneous metastasis
mimicking Mondor disease as an important differential diagnostic consideration. A skin biopsy, in the
appropriate clinical setting, may thus be necessary to
differentiate between Mondor disease and cutaneous spread of the associated cancer. Clinical features
favoring cutaneous metastasis may include prolonged duration, absence of warmth or surrounding
induration, and a bound-down lesion with lack of
mobility.
Cutaneous metastases of thyroid cancers are rare,
with the scalp being the most common site.5 Prior
morphologic descriptions of cutaneous thyroid metastasis include ulcerating blue or skin-colored papules and nodules.5 This rare case also illustrates an
unusual presentation of cutaneous metastasis of
thyroid cancer.
Faranak Kamangar, BSc,a Timothy McCalmont,
MD,b and Kanade Shinkai, MD, PhDc
University of California, San Francisco Psoriasis
Skin and Treatment Center,a UCSF Dermatopathology Service,b and UCSF Department of
Dermatologyc
Funding sources: None.
Conflicts of interest: None declared.

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VOLUME 67, NUMBER 2

Correspondence to: Kanade Shinkai, MD, PhD,

Assistant Professor of Clinical Dermatology,
UCSF Department of Dermatology, 1701 Divisadero St, San Francisco, CA 94115
E-mail: ShinkaiK@derm.ucsf.edu
REFERENCES
1. Levi I, Baum M. Mondors disease as a presenting symptom of
breast cancer. Br J Surg 1987;74:700.
2. Alvarez-Garrido H, Garrido-Rios AA, Sanz-Munoz C, MirandaRomero A. Mondors disease. Clin Exp Dermatol 2009;34:753-6.
3. Courtney SP, Polacarz S, Raftery AT. Mondors disease associated with metastatic lung cancer in the breast. Postgrad Med J
1989;65:779-80.
4. Soler-Gonzalez J, Ruiz MC. Images in clinical medicine. Mondors disease. N Engl J Med 2005;352:1024.
5. Nashed C, Sakpal SV, Cherneykin S, Chamberlain RS. Medullary
thyroid carcinoma metastatic to skin. J Cutan Pathol
2010;37:1237-40.
http://dx.doi.org/10.1016/j.jaad.2011.09.017

Combination therapy of imiquimod and

gentian violet for cutaneous melanoma
metastases
To the Editor: The patient was a 92-year-old white
man with significant history of anemia of chronic
disease with probable hemolysis from metallic aortic
valve, requiring anticoagulation with warfarin. He
also had gastric antral vascular ectasia and chronic
kidney disease, leading to continuous bleeding. He
received periodic blood transfusions as well as
epoetin alpha and darbepoetin alpha. Seven years
before treatment, he was noted to have marginal
zone lymphoma, stage IVA (CD201). Ten months
before treatment, he was noted to have an exophytic
growth on his scalp. Biopsy specimen revealed
melanoma, with a Breslow thickness of at least 6.1
mm, 20 mitosis per high-powered field, extensive
ulceration, and angiolymphatic invasion. The lesion
was negative for microsatellites. Thus, the tumor,
using American Joint Committee on Cancer staging,
was pT4bN0. Staging workup at this time using
positron emission/computerized tomography revealed bilateral cervical adenopathy and pulmonary
nodules less than 1 cm in diameter. The lesion was
excised, but rapidly recurred. The patient received
radiation therapy to his scalp lesion, followed by
regression of the scalp lesion.
At the time of presentation, 6 months after radiation therapy, he presented with 3 crusted lesions in
the scalp, ranging in size from 1.5 to 4.5 cm in
diameter (Fig 1, A). The lesions were anesthetized,
debulked, and curetted, followed by cryotherapy of
the base of each lesion for 30 seconds with a rapid
movement, so as to rapidly obtain frosting. The halo

Letters e81

was maintained by rapid movement of the cryotherapy apparatus to keep the halo for 30 seconds,
followed by a 2.5-minute thaw (Fig 1, B). The size of
the halo corresponded to the size of the debulked
lesions. Upon thawing, 1% gentian violet was applied to the wounds, and the patient was instructed
to apply gentian violet and imiquimod to the base of
the lesions daily. This was accompanied by a brisk
inflammatory response. At the time of reexamination, 4 months after the procedure, no
clinical recurrence was noted. The largest lesion
was replaced by a depressed scar (Fig 1, C ).
Cutaneous metastasis is a common sequelae of
advanced melanoma. We present a novel palliative
method for the treatment of this complication in a
patient with significant comorbidities, including advanced age, anticoagulation for a metallic valve,
chronic anemia, macular degeneration, and history
of hematopoietic malignancy (high-grade lymphoma, Waldenstr
om macroglobulinemia). We do
not claim to have cured the patient, as he likely has
distant disease not amenable to local treatment.
However, the lack of recurrence after 6 months is
remarkable for the following reasons. When the
patient had a solitary lesion, recurrence after both
surgery and radiation therapy occurred before 4
months, but we have not observed recurrence yet in
this patient. Second, our therapy most likely did not
eradicate every single melanoma cell on the scalp.
Given that the original tumors were highly mitotic,
it is likely that residual tumor cells were left (Fig 2).
The lack of recurrence points toward a potential
immune role in tumor elimination. Third, we observed a brisk inflammatory response to the combination of gentian violet and imiquimod. Given that
gentian violet is usually anti-inflammatory, we were
surprised by this response. One potential explanation is that gentian violet is an angiogenesis inhibitor,
and angiogenesis inhibitors have been found to
potentiate immune responses because of reversal
of vascular endothelial growth factoremediated
inhibition of dendritic cell maturation.1
Imiquimod has previously been used as monotherapy for both lentigo maligna and melanoma
metastases, with mixed results. In treatment of
patients with lentigo maligna, regression of thin
lesions are sometimes seen, but nodules of invasive
tumor are often left behind.2,3 Similar findings have
been observed in metastatic nodules.4 The reasons
for failure of imiquimod monotherapy in melanoma
are poorly understood, but we hypothesize two
potential mechanisms. The first is of delivery. It is a
major challenge for a topically applied drug to reach
parts of either a lentigo maligna or a dermal melanoma nodule. Second is the possibility that