J AM ACAD DERMATOL Case reports 757

VOLUME 49, NUMBER 4

We thank Dr David Scollard for his contribution and
the Hansen’s Disease Center in Baton Rouge, La.
REFERENCES
1. Inamadar AC, Sampagavi VV. Concomitant occurrence of leprosy,
cutaneous tuberculosis and pulmonary tuberculosis–a case re-
port. Lepr Rev 1994;65:282-5.
2. Gatner EMS, Glatthaar E, Imkamp FMJH, Kok SH. Association of
tuberculosis and leprosy in South Africa. Lepr Rev 1980;51:5-10.
3. Kumar B, Kaur S, Kataria S, Roy SN. Concomitant occurrence of
leprosy and tuberculosis–a clinical, bacteriological and radiolog-
ical evaluation. Lepr India 1982;54:671-6.
4. Nigam P, Dubby AL, Dayal SG, Goyal BM, Saxena HN, Samuel KC.
The association of leprosy and pulmonary tuberculosis. Lepr In-
dia 1979;51:65-73.
5. Lietman T, Porco T, Blower S. Leprosy and tuberculosis: the epi-
demiological consequences of cross-immunity. Am Pub Health
1997;87:1923-7.
6. Fernandez JM. Leprosy and tuberculosis. Arch Dermatol 1957;75:
101-6.
7. Karonga Prevention Trial Group. Randomized controlled trial of
single BCG, repeated BCG, or combined BCG and killed Mycobac-
terium leprae vaccine for prevention of leprosy and tuberculosis
in Malawi. Lancet 1996;348:17-24.
8. Husser JA, Traore I, Daumerie D. Activity of two doses of rifampin
against Mycobacterium leprae. Int J Lepr 1994;62:359-64.
9. Jacobson R, Krahenbuhl J. Leprosy (seminar). Lancet 1999;353:
655-60.

Cutaneous metastasis of osteosarcoma

De Anne H. Collier, MD,a Klaus Busam, MD,b and Stacy Salob, MDa,c
New York, New York

Cutaneous metastases of solid tumors have been reported with a frequency that ranges from 0.7% to 4.4%
with recent studies reporting 9% and 10%. Osteosarcomas seldom metastasize to the skin. The most
frequent metastatic sites are to the lungs, bones, and kidneys. We report 2 cases of osteosarcoma that
metastasized to the skin. A 75-year-old patient with known osteosarcoma of the tibia developed cutaneous
nodules overlying the site of the primary tumor. A 46-year-old woman with a history of osteosarcoma of the
knee developed a nodule on her scalp. Histologic examination of both lesions revealed metastatic
osteosarcoma. This is a rare event that, to our knowledge, has previously only been reported 6 times. (J Am
Acad Dermatol 2003;49:757-60.)

C utaneous metastases of solid tumors have

been reported with a frequency of 0.7% to
4.4% on the basis of autopsy studies.1-5 How-
ever, 2 recent studies have demonstrated cutaneous
metastases to be a more frequent occurrence. A
series of 7518 autopsy cases revealed 679 cases of
cutaneous metastases (9%).6 In a review of 4020
patients with metastatic cancer, Lookingbill et al7
found 420 patients with cutaneous metastases
(10%). In their series, melanoma, breast cancer, and
cancers of the upper respiratory tract (oral cavity,
From the Department of Dermatology, Weill Medical College of
Cornell University, New York Presbyterian Hospital,a the
Department of Pathology,b and Division of Dermatology,c
Memorial Sloan-Kettering Cancer Center.
Funding sources: None.
Conflicts of interest: None disclosed.
Reprint requests: Stacy Salob, MD, 351 E Main St, Mt Kisco, NY
10549.
Copyright © 2003 by the American Academy of Dermatology, Inc.
0190-9622/2003/$30.00 ⫹ 0
doi:10.1067/S0190-9622(03)00460-2
nasal sinuses, and larynx) were the neoplasms that
most frequently metastasized to the skin.
Osteosarcoma can occur at any age, although it is
most common in children and young adults. The
mean age is 25 years in male and female patients,
whereas the median age is 17 to 18 years.8 The
diagnosis of primary osteosarcoma in older patients
should be accepted only after careful examination
excludes association with other pre-existing bone
diseases such as Paget’s disease and fibrous dyspla-
sia. The long bones of the extremities are the most
common sites of osteosarcoma, with the femur in-
volved in 44%, the tibia in 17%, and the humerus in
15%.8
Osteosarcoma tends to metastasize by the hema-
togenous route primarily to the lungs. At autopsy,
the most frequent metastatic sites are the lungs
(95%), bones (50%), and kidneys (12%).8 Metastases
to the skin are exceedingly rare and a review of the
literature disclosed only 6 previous reports. We re-
port 2 cases in which patients had evidence of both
cutaneous and pulmonary metastases.
758 Case reports
CASE REPORTS
Case 1
The patient was a 75-year-old Polish woman with
a medical history of hypertension who presented to
her primary care clinic in February 1999 with 1 to 2
years of bilateral foot pain and associated edema.
Radiographs of the bilateral feet were unremarkable.
Although she had no associated right knee pain,
radiograph of the right knee showed a large tumor.
The patient was referred to a tertiary academic cen-
ter for further treatment.
At the time of the initial consultation, she de-
scribed symptoms of pain in the right proximal tibia
and a history of multiple falls on the right knee
during the past decade. On physical examination,
the proximal tibia demonstrated a mass that was
slightly warm. A core biopsy specimen of the right
tibia in March 1999 was positive for osteosarcoma.
Chest radiograph showed 2 small lesions in the
lungs suggestive of pulmonary metastases. The pa-
tient received 2 cycles of doxorubicin and cisplatin
neoadjuvantly before having an end-block resection
of her right proximal tibia with total knee replace-
ment and tumor resection in July 1999. Pathology
confirmed the diagnosis of osteogenic sarcoma,
high-grade osteoblastic and fibroblastic types. The
tumor extended into the cruciate ligament and ad-
jacent soft tissue including tendons, skeletal muscle,
and adipose tissue. The skin was unremarkable. The
margins were reported to be free of disease. Ap-
proximately 40% of the tumor showed necrosis with
grade II response to chemotherapy.
Postoperatively, the patient began having in-
creasing pain and, in October 1999 a right knee
radiograph demonstrated multiple calcifications
around the distal femur and proximal tibia. A re-
peated chest radiograph demonstrated significantly
increased calcified nodules in the both lungs. A
bone scan demonstrated uptake in multiple lung
nodules and in the right knee. At this time the pa-
tient presented to our institution for consultation
regarding systemic chemotherapy.
The patient had stage IV metastatic osteogenic
sarcoma of the right proximal tibia with pulmonary
metastases and local recurrence at the site of resec-
tion. Systemic chemotherapy was recommended
and the patient received ifosfamide. During her ad-
mission for her fourth cycle of chemotherapy, it was
noted that the patient had asymptomatic skin lesions
on the right knee. Examination revealed multiple,
6-mm, erythematous, nontender dermal nodules
overlying the anterior and posterior knee and distal
thigh (Fig 1). A skin punch biopsy specimen re-
vealed a dense infiltration of the dermis by tumor
J AM ACAD DERMATOL
OCTOBER 2003
Fig 1. Erythematous firm dermal nodules overlying distal
thigh.
cells. The tumor cells were pleomorphic and mitot-
ically active. Focally osteoid matrix was identified.
The patient continued to receive additional cycles
of ifosfamide, and some of the skin lesions regressed
although others were stable or slightly larger in size.
However, chemotherapy was discontinued second-
ary to elevated creatinine. The patient had progres-
sion of disease with the development of painful
subcutaneous nodules in the scalp, which were pre-
sumed to be metastatic disease. The patient deferred
further chemotherapy and was subsequently lost to
follow-up.
Case 2
The patient was a 46-year-old woman who was
originally diagnosed with osteogenic sarcoma in
1976 while undergoing workup for torn cartilage in
her right knee. In 1976 she had several operations in
which the tumor was partially resected. In Novem-
ber 1977, the patient underwent block resection of
the distal right femur and right knee joint with in-
sertion of knee prosthesis. The pathology of this
tumor was a low grade, juxtacortic osteogenic sar-
coma.
The patient received no adjuvant chemotherapy
at that time. She was followed up for 20 years with-
out evidence of disease. However, in February 1998
she noticed an increasing mass at the posterior as-
pect of the right distal thigh. Resection of the tumor
demonstrated focally high-grade osteogenic sar-
coma arising within a predominantly low-grade os-
teosarcoma (90%-95%) measuring 9 cm in its great-
est dimension, involving the skeletal muscle and soft
tissues. The margins were free of tumor.
Because of evidence of high-grade disease, sys-
temic chemotherapy was recommended. The regi-
men consisted of high-dose methotrexate, ifosf-
amide, doxorubicin, and cisplatin and was
completed in December 1998. In April of 1999, the
patient had recurrence of a posterior thigh mass and
underwent subsequent surgical resection, again
J AM ACAD DERMATOL
VOLUME 49, NUMBER 4
Fig 2. Metastatic osteosarcoma in dermis and subcutis (A) and lung (B). (Hematoxylin-eosin
stain; original magnification ⫻10.)
demonstrating low-grade osteogenic sarcoma in-
volving soft tissue, within one high-power field of a
major nerve trunk with focal high-grade osteosar-
coma. Further resection 1 month later revealed re-
current low-grade osteogenic sarcoma invading the
sciatic nerve. Margins were not involved. In Febru-
ary 2000, the patient presented to her dermatology
deparrtment with a growth on the scalp of 4 months’
duration. A recent computed tomography (CT) scan
at this time also revealed new bilateral pulmonary
nodules, thought to be metastatic disease. Bone scan
also demonstrated uptake in the thorax.
The patient underwent an excisional biopsy of
the scalp lesion. A frozen section was performed at
the surgeon’s request and an instant diagnosis of
metastatic osteosarcoma was made. The histologic
findings of the biopsy specimen revealed a dermal
and subcutaneous nodule composed of osteoid ma-
trix surrounded by a spindle cell proliferation and
associated inflammation (Fig 2, A). The tumor in the
skin was identical in appearance to a right lung
metastasis, which was subsequently resected (Fig 2,
B). In May 2000, the patient had a chest CT scan that
demonstrated a calcified lesion in the left apex
thought to represent either a rib exostosis or a met-
astatic deposit. In addition, a lesion in the right
lower lobe suggestive of metastatic lesion or scar
tissue from the previous wedge resection in this area
was also seen on CT scan. The patient had monthly
Case reports 759
CT scans that demonstrated new bilateral pulmonary
nodules thought to represent metastases. The pa-
tient was treated with trimetrexate, which was sub-
sequently discontinued after 1 month secondary to
nausea. The patient was placed on aerosolized
Adriamycin and has been followed up closely for
signs of toxicity and progression of disease.
DISCUSSION
Cutaneous metastases occur most commonly as
multiple nodules in the vicinity of the primary tu-
mor.9 The patient in case 1 clearly demonstrated this
phenomenon. Like the patient in case 2, nodules
subsequently developed on her scalp, signifying dis-
tant metastases. Distant metastases are not rare and
occurred in 39% of Lookingbill et al’s7 retrospective
study of cutaneous metastases.
Review of the literature disclosed only a few in-
stances of cutaneous metastases of osteosarcoma.
Skin metastases were first demonstrated in 1924,
when a primary tumor on the right humerus had
metastasized to the scalp and left submaxillary re-
gion before spreading to the lung and pleura.10
Brownstein and Helwig11 reviewed 724 cases of cu-
taneous metastases, 19 of which resulted from a
metastatic sarcoma. This group included a variety of
soft-tissue and bone sarcomas, but no details are
given of the actual number of patients with osteo-
sarcoma. In this series, sarcomas with cutaneous
760 Case reports
metastases represented 3% of all cutaneous metas-
tases in men and 2% in women. Jeffree et al12 de-
scribed 2 patients with subcutaneous metastases and
1 patient with scalp metastasis resulting from osteo-
sarcoma in an analysis of 152 cases of clinically
evident metastatic osteosarcoma (including 43 au-
topsy cases). In this series, more than 90% of pa-
tients had lung metastases. In an analysis of 7518
autopsy cases, Spencer and Helm6 reported 13 pa-
tients with primary tumors of bone and muscle who
had skin metastases. It is unclear whether osteosar-
coma was one of these primary tumors. Myhand et
al13 recently reported a patient with osteosarcoma of
the right clavicle with overlying cutaneous metasta-
sis. Setoyama et al14 reported a case in which a
patient with osteosarcoma originating in the right
humerus developed cutaneous metastasis on the
temple.
In our 2 cases, cutaneous metastases were seen
along with pulmonary metastasis. In case 1, the
cutaneous metastasis was originally seen overlying
the primary tumor, but subcutaneous scalp nodules
developed that were presumed to be scalp metasta-
ses. In case 2, the cutaneous metastasis was distant
from the primary site. The means by which osteo-
sarcoma metastasizes to a distant cutaneous site is
not well delineated. Because lymphatic involvement
was not evident in our patient, cutaneous metastasis
most likely resulted from hematogenous dissemina-
tion. The general pattern found in autopsy studies
indicates that hematogenous dissemination of tumor
is usual. Lymph node involvement is present clini-
cally in only 10% of patients, although autopsy stud-
ies show that a higher incidence, up to 50%, may
occur.15
The biologic basis of tumor metastasis is com-
plex. Dissemination may take place hematog-
enously or through the lymphatics. A tumor needs to
be able to detach and circulate in the blood, reattach
in a distant site, and finally grow at the new site.
Tumors that tend to invade veins such as carcinoma
of the kidney and lung often present as cutaneous
metastases at a distance from the primary tumor,
through hematogenous dissemination. Cancers that
follow the primary tumor, appearing in the overlying
skin, spread largely through lymphatic channels. In
carcinomas of the breast, metastases appear in the
overlying skin through the lymphatic channels.16
Both of our patients had distant metastases involving
the scalp. The vascularity and immobility of the
J AM ACAD DERMATOL
OCTOBER 2003
scalp may be a contributing factor, and possible
dissemination through the valveless vertebral ve-
nous system that includes the epidural veins, periv-
ertebral veins, and veins of the head and neck.2,17 A
review by Schwartz17 revealed cutaneous metastases
were often identified before primary tumor in carci-
noma of the kidney and lung because early venous
invasion through channels including the vertebral
venous system may take the metastasis to a distant
site. Early identification of cutaneous metastases
may allow for early diagnosis, implementation of
therapy, and possible prolonged survival.
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patients. J Am Acad Dermatol 1993;29:228-36.
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10. Finnerud CW. Ossifying sarcoma of the skin metastatic from os-
sifying sarcoma of the humerus. Arch Dermatol 1924;10:56-62.
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cer 1972;29:1298-307.
12. Jeffree GM, Price CHG, Sissons HA. The metastatic patterns of
osteosarcoma. Br J Cancer 1975;32:87-107.
13. Myhand RC, Hung P-H, Caldwell JB, James WD, Sau P, Hargis JB.
Osteogenic sarcoma with skin metastases. J Am Acad Dermatol
1995;32:803-5.
14. Setoyama M, Kanda A, Kanzaki T. Cutaneous metastasis of an
osteosarcoma: a case report. Am J Dermatopathol 1996;18:629-
32.
15. Caceres E, Zaharia M, Calderon R. Incidence of regional lymph
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Oncol 1990;6:231-3.
16. Johnson WC. Metastatic carcinoma of the skin. In: Elder D, Eleni-
sas R, Jaworsky C, Johnson B, editors. Lever’s histopathology of
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tol 1995;33:161-82.