Gynecologic Oncology Reports 2 (2012) 124–126
Contents lists available at SciVerse ScienceDirect
Gynecologic Oncology Reports
j ourna l homepage: www.e lsev ie r .com/ locate /gynorCase Report
Management of a skin metastasis in a patient with advanced ovarian cancer
Andrew C. Wiechert a,b,⁎, Leslie A. Garrett b, George Lin c, Annekathryn Goodman b
a Brigham & Women's Hospital, Department of Obstetrics, Gynecology and Reproductive Biology, 75 Francis Street, ASB1-3-078, Boston, MA 02115, USA
b Massachusetts General Hospital, Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, 55 Fruit Street, Boston, MA 02114, USA
c Brigham & Women's Hospital, Department of Pathology, 75 Francis Street, Boston, MA 02115, USAa r t i c l e i n f oArticle history:
Received 22 May 2012
Accepted 24 July 2012
Available online 1 August 2012
Keywords:
Ovarian cancer
Cutaneous metastases
PalliationTable 1
Treatment timeline.
Time since Symptom Intervention
diagnosis (months)
0 Abdominal distention Surgery; carboplatin/
taxol×6 cycles
12 Biopsy-proven nodal Weekly paclitaxel
recurrence
21 Progressive Doxorubicin
lymphadenopathy
25 Increased retroperitoneal Doxorubicin+3G3Introduction
Recurrent ovarian cancer most commonly presents with intra-
peritoneal or intra-abdominal lymphatic metastases. Unusual sites of
progressive or metastatic disease have been reported either in women
whohave beenheavily pretreated orwho recur after a prolonged disease
free interval (Dauplat et al., 1987). The classic presentationwith a “Sister
Mary Joseph node” at the umbilicus from intra-abdominal extension via
lymphatics is a well known example of skin metastases (Tourad et al.,
2000). However, diffuse skin metastases in other locations are unusual.
We describe a patient whose progressive ovarian cancer manifested as
a pruritic rash and review the literature on this topic.
Case report
A 54 year old Caucasian woman presented to her oncologist
complaining of a pruritic rash that had developed along her inguinal
fold and the vulvo-vaginal area. At age 50 she was diagnosed with syn-
chronous stage IIC high-grade endometrioid ovarian adenocarcinoma
and a stage IIA low-grade endometrioid endometrial adenocarcinoma.
After optimal cytoreductive surgery, she received six cycles of intrave-
nous carboplatin and paclitaxel chemotherapy. Biopsy-proven disease
recurrencewas detected by CT scan 12 months after completing prima-
ry therapy, and she began treatmentwithweekly paclitaxel. Progressive⁎ Corresponding author at: Department of Obstetrics & Gynecology, Brigham &
Women's Hospital, 75 Francis Street, ASB 1-3-078, Boston, MA 02115, USA.
E-mail address: awiechert@partners.org (A.C. Wiechert).
2211-338X/$ – see front matter © 2012 Elsevier Inc. All rights reserved.
http://dx.doi.org/10.1016/j.gynor.2012.07.003lymphadenopathy along the left common iliac nodes was detected
9 months later and the patient switched to single-agent doxorubicin
as part of a randomized clinical trial. Four months later, and 13 months
after the initial cancer recurrence, a CT scan demonstrated increased
retroperitoneal lymphadenopathy and the patient crossed-over to re-
ceive the experimental arm of the trial, receiving doxorubicin plus
3G3, a monoclonal antibody therapy (Shah et al., 2010). Disease pro-
gression led to Avastin with metronomic cyclophosphamide, on which
she wasmaintained with good effect for another 10 months when pro-
gressive disease necessitated a switch to carboplatin and gemcitabine.
Table 1 outlines the time line of her disease recurrences and the differ-
ent types of therapy that she received.
The patient presented to her oncologist complaining of a new intense-
ly pruritic, erythematous, maculo-papular rash that had developed over
the course of a few weeks along her left inner thigh, and extended
along the inguinal fold to the left labia majora and mons pubis (Fig. 1).
She had no personal history of dermatologic conditions, including psoria-
sis. The patient was referred to Dermatology after experiencing no relief
from topical steroids and anti-fungal ointments and a punch biopsy of
the skin showed malignant cells.
The patient had concurrent intraperitoneal disease progression at
the time of her diagnosed skin lesion, and was offered conversion to
chemotherapy with carboplatin and gemcitabine. The patient was re-
ferred to radiation oncology, where it was recommended she undergo
local external beam radiation therapy to the site of skin metastasis for
palliative treatment. She received 400 cGy fractions twice weekly for
a total dose of 2400 cGy. On follow-up this appeared to have littlelymphadenopathy
27 Progression Avastin and metronomic
cyclophosphamide
37 Peritoneal thickening and Carboplatin and gemcitabine
skin metastasis
A.C. Wiechert et al. / Gynecologic Oncology Reports 2 (2012) 124–126 125
Fig. 1. The erythematous rash began as seen here and extended to the mons pubis
along the inguinal fold.impact on her local disease burden, which was noted still to be easily
palpable 6 weeks after treatment. She was also treated with Paroxetine
and Mirtazipine therapy for control of the pruritus. Over a gradual
period of approximately 6 weeks she noted substantial improvement
in her symptoms from the combination of medications and radiation.
The patient's clinical course deteriorated with progression of her
intra-abdominal disease, and she withdrew from curative therapy to
enroll in a comprehensive palliative care program, of which these ther-
apies were a part. She passed away from complications of her disease
10 months after her skin metastasis was diagnosed.A
C
Fig. 2. A: H&E 100×; B: CA-125 positive 100×; C:Pathology
The punch biopsy showed a poorly differentiated adenocarcinoma
present in the dermis with extensive lymphovascular invasion. Im-
munohistochemical stains revealed that the tumor is positive for
CK7 and CA-125 and negative for CK20 (not shown), CDX-2, and
WT-1 (not shown). The immunohistochemistry stains of the skin me-
tastasis match the ascites drained at the time of the ovarian
debulking, and the poorly differentiated morphology is consistent
with metastasis from the patient's known endometrioid adenocarci-
noma. While IHC stains were not initially done on each of the
patient's two primary tumors, the morphology of the metastasis is
much more similar to the ovarian tumor and is much more likely to
be an ovarian metastasis, as opposed to a poorly-differentiated me-
tastasis of the synchronous low-grade endometrial tumor (Fig. 2).Discussion
Ovarian cancer remains the leading cause of death among gyneco-
logic cancers (Howlader et al., 2011). Patterns of metastasis in ovarian
carcinoma are well described (Dauplat et al., 1987). Intra-abdominal
spread along the peritoneum and encasement of the intra-peritoneal
structures is most commonly seen along with pelvic and para-aortic
lymphatic involvement at advanced stages. The most common site of
extra-peritoneal involvement is the lung, with right-sided pleural effu-
sion being themost common clinicalfinding to qualify a patient as Stage
IV disease (Dauplat et al., 1987).
Cutaneous disease, by contrast, is quite uncommon. In a case series of
nine patients fromover 200 treated at a single center in Italy, Cormio et al.
detected a rate of 3.5% for metastasis to the skin (Cormio et al., 2003).
Many of the reported cases present as nodular lesions, commonly onB
D
CK7 positive 100×; D: CDX 2 negative 100×.
126 A.C. Wiechert et al. / Gynecologic Oncology Reports 2 (2012) 124–126the abdomen or thorax (Cowan et al., 1995), and commonly at or around
abdominalwall incisions, either laparotomy or laparoscopy scars (Cormio
et al., 2003).
Because skin metastases commonly present in the setting of
advanced-stage, metastatic disease, the prognosis is poor (Tourad et
al., 2000; Cormio et al., 2003; Cowan et al., 1995). In the series of
nine patients by Cormio, the median survival after presentation of
skin metastasis was 4 months (range 2–65 months). The small num-
bers make comparison difficult between skin metastasis and other
presentations of advanced ovarian cancer, but comparing to malig-
nant small bowel obstruction, for example, with a median overall sur-
vival of 7 months (Sartori et al., 2010), skin metastasis could be seen
as a marker of poor prognosis.
There are no published protocols for the treatment of isolated
ovarian skin metastasis. In a case report from Turkey (Demirci et al.,
2010), a 43-year-old patient with isolated abdominal wall metastases
was treated with 37.5 Gy in 2.5 Gy/day fractions of external beam ra-
diation therapy. In follow-up she was noted to have tumor regression
and was still alive at 7 months of follow-up.
In the case series from Cormio, patients who presented with skin
metastasis as manifestation of recurrence were treated with chemo-
therapy with or without surgical resection of the lesion. Patients with
surgical resection of their disease had a median survival of 35 months
(range 25–65) while patients treated with chemotherapy only live a
median of 2 months (range 1–3) (Cormio et al., 2003). It appears that
surgical resection may offer a survival advantage, but these data were
not randomized and presumably there were clinical differences that
precluded surgical resection in the patients treated with chemotherapy
alone. Further study is warranted to determine the value of surgical re-
section for cutaneous metastasis of ovarian cancer.
Treatment of this patient's severe localized pruritis also proved diffi-
cult. Pruritis has been reported as a presenting complaint of many solid
tumors, including scrotal itch (prostate cancer), itchy nares (brain tu-
mors), vulvar itch (cervical cancer) and peri-anal itch (rectal or sigmoid
colon cancer) (Twycross et al., 2003). In the case of itch caused by ma-
lignant cell invasion of tissue, the physiologic mechanism is speculated
to be release of irritating chemokines including histamine, IL-2, and pa-
pain. These substances trigger stimulation of a subset of nerves called
C-fibers, which transmit the signal from the pruritogen to the central
nervous system, triggering awareness of the sensation. Some data
exist for the use of paroxetine therapy to decrease pruritis symptoms
however this appears to be a short-term benefit (Krajnik and Zylicz,
2001). Other localized therapy, including moisturizers to prevent dry
skin, and treatment such as external beam radiation therapy to reduce
the presence of disease at the site of pruritus is indicated as well. Ofnote, 2 months after our patient underwent radiation therapy; her pru-
ritus had diminished significantly despite a persisting palpable disease
burden. The mechanism for this improvement is unclear.
Summary
Cutaneous metastasis of ovarian epithelial adenocarcinoma is rare.
Treatment strategies depend on the associated disease burden, but for
treatment of the skin lesion itself, roles have been suggested for
multi-modal therapy including surgical resection of nodular disease,
systemic chemotherapy, and external beam radiation therapy to the
site of metastasis. Overall, the prognosis remains poor. Attention
should be paid to palliation of symptoms caused by the lesions, in-
cluding pruritus. Local topical treatments, local radiation therapy, and
orally-administered anti-serotonergic therapy also have been reported
to have some success.
Conflict of interest statement
The authors declare that there are no conflicts of interest.
References
Cormio, G., Capotort, M., Di Vagno, G., Cazzolla, A., Carriero, C., Carriero, C., Selvaggi, l.,
2003. Skin metastases in ovarian carcinoma: a report of nine cases and a review of
the literature. Gynecol. Oncol. 90 (3), 682–685.
Cowan, L.J., Roller, J.I., Connelly, P.J., Nahhas, W.A., 1995. Extraovarian stage IV perito-
neal serous papillary carcinoma presenting as an asymptomatic skin lesion – a
case report and literature review. Gynecol. Oncol. 57 (3), 433–435.
Dauplat, J., Hacker, N.F., Nieberg, R.K., Berek, J.S., Rose, T.P., Sagae, S., 1987. Distant
metastases in epithelial ovarian carcinoma. Cancer 60, 1561–1566.
Demirci, S., Yavas, F., Ozsaran, Z., Ozsaran, A., Dikmen, Y., Zekioglu, O., Karabulut, B.,
Aras, A.B., 2010. Palliative radiotherapy for the skin metastasis of ovarian cancer:
a case report and review of the literature. Med. Oncol. 27 (3), 628–631.
Howlader, N., Noone, A.M., Krapcho, M., Neyman, N., Aminou, R., Waldron, W.,
Altekruse, S.F., Kosary, C.L., Ruhl, J., Tatalovich, Z., Cho, H., Mariotto, A., Eisner,
M.P., Lewis, D.R., Chen, H.S., Feuer, E.J., Cronin, K.A., Edwards, B.K. (Eds.), 2011.
SEER Cancer Statistics Review, 1975–2008. National Cancer Institute, Bethesda,
MD. http://seer.cancer.gov/csr/1975_2008/, based on November 2010 SEER data
submission, posted to the SEER web site.
Krajnik, M., Zylicz, Z., 2001. Understanding pruritus in systemic disease. J. Pain Symp-
tom Manage. 21, 151–168.
Sartori, E., Chiudinelli, F., Pasinetti, B., Sostegni, B., Maggino, T., 2010. Possible role of
palliative surgery for bowel obstruction in advanced ovarian cancer patients.
Eur. J. Gynaecol. Oncol. 21 (1), 31–36.
Shah, G.D., Loizos, N., Youssoufian, H., Schwartz, J.D., Rowinsky, E.K., 2010. Rationale for
the development of IMC-3G3, a fully human immunoglobulin G subclass 1 mono-
clonal antibody targeting the platelet-derived growth factor receptor alpha. Cancer
116 (4 supplement), 1018–1026.
Tourad, J.P., Lentz, N., Dutronc, Y., Mercier, E., Sagot, P., Lambert, D., 2000. Umbilical
cutaneous metastasis (or Sister Mary Joseph's nodule) disclosing an ovarian ade-
nocarcinoma. Gynecol. Obstet. Fertil. 28 (10), 719–721.
Twycross, R., Greaves, M.W., Handwerker, H., Jones, E.A., Libretto, S.E., Szepietowski,
J.C., Zylicz, Z., 2003. Itch: scratching more than the surface. Q. J. Med. 96, 7–26.