Supraclavicular metastases from a sex cord stromal tumor of the ovary.
ABSTRACT Metastases to the supraclavicular fossa usually originate from head and neck or infraclavicular tumors. Ovarian primaries of supraclavicular metastases are very rare. Sex cord stromal tumors of the ovary account for 5-8% of all ovarian malignancies and there have been only a few case reports on distant metastases from these tumors. A 46-year-old woman presented to us with a left supraclavicular mass. She had had a sex cord stromal tumor in the right ovary four years before. Comprehensive clinical investigation and fine-needle aspiration cytology were performed. The lesion had the characteristics of a sex cord stromal tumor. To our knowledge, this is the first report of such a case in the English literature. We discuss its pathological and clinical features in the light of the current knowledge.
Article: Granulosa cell tumours of the ovary.[Show abstract] [Hide abstract]
ABSTRACT: Granulosa cell tumours are rare, potentially malignant sex cord stromal tumours of the ovary. They are unique in their presentation and histological features. Many of them are hormone-producing and this property helps them to present early unlike other epithelial ovarian cancers. As a result, most of them will be in an early stage at the time of initial diagnosis. The tumour can manifest in young girls as a juvenile form and conservative management with unilateral salpingo-opherectomy may be an option in them as 95% are unilateral. Surgery is the treatment of choice and initial staging laparatomy a determinant recurrence. Advance stage of the tumour, its size (>5 cm), mitotic figures (>10/hpf), nuclear atypia and absence of call-exner bodies are poor prognostic factors. Such tumours are characterised by late recurrences and this necessitates a prolonged follow-up. Tumour markers such as inhibin and estradiol are useful in follow-up. Chemotherapy, radiotherapy and hormone replacement therapy have very little role in the initial treatment and may be suggested in case of recurrences. With appropriate treatment, a better survival rate can be achieved as against other ovarian malignancies. Methods used for locating, selecting and synthesising data: A search of Medline and Cochrane data base for the period from 1999 to 2010 was carried out to include relevant systematic reviews, meta-analysis, randomised controlled and other clinical and rare case reports. The date of the last search was January 2010.Australian and New Zealand Journal of Obstetrics and Gynaecology 06/2010; 50(3):216-20. · 1.30 Impact Factor
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ABSTRACT: Ovarian sex-cord stromal tumor (SCST) comprises 5% of the ovarian neoplasm; it occurs as an ovarian mass or hemoperitoneum, and the surgical management of SCST is not well defined at early stage and in adult patients. The authors tested to test the total not radical laparoscopic management of SCST in postmenopausal women at early stage. Three postmenopausal women were admitted in University-affiliated hospitals for pelvic pain, ovarian complex mass and genital bleeding. Preoperative clinical and instrumental examination suspected an ovarian tumor; therefore, a total laparoscopic approach was attempted. All patients underwent laparoscopic oophorectomy with the frozen section, who suggested for ovarian SCST; one woman received a total laparoscopic hysterectomy plus other oophorectomy, two received only the complementary oophorectomy, all without intensive surgical staging by with pelvic and para-aortic lymphadenectomy, appendectomy, peritoneal biopsies, and omentectomy. All patients completed surgery without intrasurgical and postsurgical complications, with a fast dismissal. They are, currently, in long-term follow-up, with a 100% of survival after 3 years and with none morbility and morbidity. In order to fast restore and preserve women's integrity, total laparoscopic approach of early SCST in adult age, without intensive radical staging, could be an appropriate clinical choice, since these tumors at slow growth, recurring locally and only a long time after initial treatment. This minimally invasive management could be suggested in association with a long-term follow-up, as possible "wait and see" postoperative option.Archives of Gynecology 11/2010; 283 Suppl 1:87-91. · 0.91 Impact Factor
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ABSTRACT: Granulosa cell tumors (GCTs) are the most common ovarian estrogen producing tumors, leading to symptoms of excessive estrogen such as endometrial hyperplasia and endometrial adenocarcinoma. These tumors have malignant potential and often recur. The etiology of GCT is unknown. TGFα is a potent mitogen for many different cells. However, its function in GCT initiation, progression and metastasis has not been determined. The present study aims to determine whether TGFα plays a role in the growth of GCT cells. KGN cells, which are derived from an invasive GCT and have many features of normal granulosa cells, were used as the cellular model. Immunohistochemistry, Western blot and RT-PCR results showed that the ErbB family of receptors is expressed in human GCT tissues and GCT cell lines. RT-PCR results also indicated that TGFα and EGF are expressed in the human granulosa cells and the GCT cell lines, suggesting that TGFα might regulate GCT cell function in an autocrine/paracrine manner. TGFα stimulated KGN cell DNA synthesis, cell proliferation, cell viability, cell cycle progression, and cell migration. TGFα rapidly activated EGFR/PI3K/Akt and mTOR pathways, as indicated by rapid phosphorylation of Akt, TSC2, Rictor, mTOR, P70S6K and S6 proteins following TGFα treatment. TGFα also rapidly activated the EGFR/MEK/ERK pathway, and P38 MAPK pathways, as indicated by the rapid phosphorylation of EGFR, MEK, ERK1/2, P38, and CREB after TGFα treatment. Whereas TGFα triggered a transient activation of Akt, it induced a sustained activation of ERK1/2 in KGN cells. Long-term treatment of KGN cells with TGFα resulted in a significant increase in cyclin D2 and a decrease in p27/Kip1, two critical regulators of granulosa cell proliferation and granulosa cell tumorigenesis. In conclusion, TGFα, via multiple signaling pathways, regulates KGN cell proliferation and migration and may play an important role in the growth and metastasis of GCTs.PLoS ONE 01/2012; 7(11):e48299. · 3.73 Impact Factor
Key words: sex cord stromal tumor,
ovarian malignancy, neck metastases,
Correspondence to: Prof Dr Murat
Ünal, Mersin Universitesi Tip Fak. Has-
tanesi, KBB AD, Zeytinlibahce cad.,
33079 Mersin, Turkey.
Tel +90-324-337 43 00;
fax +90-324-337 43 05;
Received March 7, 2008;
accepted July 4, 2008.
Supraclavicular metastases from a sex cord
stromal tumor of the ovary
Onur Ismi1, Yusuf Vayisoglu1, Tuba Karabacak2, and Murat Ünal1
1Department of Otorhinolaryngology,2Department of Pathology, Mersin University School of
Medicine, Mersin, Turkey
Metastases to the supraclavicular fossa usually originate from head and neck or infr-
aclavicular tumors. Ovarian primaries of supraclavicular metastases are very rare. Sex
cord stromal tumors of the ovary account for 5-8% of all ovarian malignancies and
there have been only a few case reports on distant metastases from these tumors. A
46-year-old woman presented to us with a left supraclavicular mass. She had had a
sex cord stromal tumor in the right ovary four years before. Comprehensive clinical
investigation and fine-needle aspiration cytology were performed.The lesion had the
characteristics of a sex cord stromal tumor.To our knowledge, this is the first report of
such a case in the English literature. We discuss its pathological and clinical features
in the light of the current knowledge.
Metastases to the supraclavicular fossa can originate from head and neck and infr-
aclavicular tumors. The principal metastatic sites from the head and neck region are
the hypopharynx, tonsil and nasopharynx1. Infraclavicular primary sites are mostly
lung, breast and cervix2. Left supraclavicular lymph node enlargement can also occur
as a gastric carcinoma metastasis. Ovarian malignancies are rare primary sites for
Sex cord stromal tumors (SCSTs) are generally considered to have a low malignant
potential and a favorable prognosis.They are non-epithelial ovarian tumors originat-
ing from the sex cords or the stroma and mesenchyme of the ovary. These tumors
have been classified as granulosa stromal cell tumors, Sertoli-Leydig cell tumors, gy-
nandroblastoma, sex cord tumor with annular tubules, and unclassified3,4. SCSTs ac-
count for 5-8% of all ovarian malignancies. Granulosa cell tumors (GCTs) are low-
grade malignancies and account for approximately 70% of SCSTs. SCST may spread
by direct local extension or intraperitoneal seeding. Recurrences occur mostly in the
pelvis and abdominal cavity. The tumors may also spread hematogenously, with pa-
tients developing metastases in the lungs, liver, and brain even years after the initial
diagnosis5,6.To our knowledge, there have been no published reports on supraclavic-
ular lymph node metastases from SCST.We present the case of an adult woman who
had a GCT in the right ovary with neck metastases, and discuss its pathological and
metastatic features in the light of the current knowledge.
A 46-year-old woman was admitted to our otorhinolaryngology department with a
mass in the left neck that had been there for 1 month. She had a history of total ab-
dominal hysterectomy and bilateral salpingo-oophorectomy because of a right ovar-
ian SCST (GCT) 4 years previously. In the ear-nose-throat examination, a 3 × 3.5 cm
solid, fixed mass was found in the left supraclavicular region. Endoscopic examina-
tion of the upper airway was normal. Computerized tomography (CT) of the neck re-
SUPRACLAVICULAR METASTASES FROM AN OVARIAN TUMOR 255
vealed a 45 × 27 mm lymphadenopathy in the left supr-
aclavicular region (Figure 1). The lymphadenopathy ex-
tended into the infraclavicular region. There were mul-
tiple metastatic nodules in both lungs. Abdominal CT
revealed lymphadenopathies on both sides of the para-
aortic region. Fine-needle aspiration cytology from the
supraclavicular mass was performed. Homogeneous
eosinophilic globular material and oval cells with light
chromatin in the nuclei were seen in the cytological
specimen (Figure 2). The cells were arranged in a follic-
ular pattern and stained positive with inhibin and CD99
(Figure 3).The pathological diagnosis was in agreement
with an SCST. Histologically the lesion was reported to
ovarian mass. The patient was referred to the gynecolo-
gy and oncology department for further therapy. A cis-
platinum-based chemotherapy regimen was adminis-
tered but she died within 2 weeks due to the toxic side
effects of this therapy.
The differential diagnosis of supraclavicular lym-
phadenopathy is broad: it includes benign lym-
phadenopathy, congenital cysts and tumors, specific in-
fections, nonspecific inflammation, primary and
phadenopathy is often malignant (58-83%). It occurs
mainly on the left side7,8. Most of the metastases origi-
nate from sites other than the head and neck including
lung, breast and cervix2,7. Intra-abdominal metastases
are also located on the left side and left supraclavicular
lymph nodes may be involved in gastric carcinoma
metastasis (Virchow’s node)8.
These lesions tend to present as an asymptomatic
mass that progresses slowly and is firm on palpation.
The associated symptoms are often related to the pri-
mary site of the neoplasm and include odynophagia,
dysphonia, otalgia and weight loss. Cervical lymph
node metastases are a common feature in head and
neck malignancies and infraclavicular tumors. The ma-
jority of patients with metastases in the lower neck
(supraclavicular fossa and posterior triangle) have
squamous cell carcinoma. The next most common his-
tological diagnosis is lymphoma, followed by adenocar-
cinoma and undifferentiated carcinoma9. Other occult
malignant neoplasms such as melanomas, sarcomas
and germ cell tumors rarely metastasize to the neck.
When the enlarged nodes are in the supraclavicular re-
gion, the digestive tract, the tracheobronchial tree, the
breast, the genitourinary tract and the thyroid gland
Figure 1 - Computed tomography of the left supraclavicular mass.
Figure 2 - Tumor cells in the fine needle aspirate.
Figure 3 - Tumor cells stained with CD99 and inhibin.
256O ISMI,YVAYISOGLU, T KARABACAK, M ÜNAL
though the role of postoperative chemotherapy and ra-
diotherapy is not well defined, these treatment modali-
ties have in some cases been associated with prolonged
disease-free and overall survival4-6.
Although ovarian cancer rarely metastasizes to the
cervical lymph node chain, it should always be consid-
ered in the differential diagnosis of lymph node en-
largement in the cervical area of adult women.
1. Lindberg R: Distribution of cervical lymph node metas-
tases from squamous cell carcinoma of the upper respira-
tory and digestive tracts. Cancer, 29: 1446-1449, 1972.
2. Ellison E, LaPuerta P, Martin SE: Supraclavicular masses:
results of a series of 309 cases biopsied by fine needle aspi-
ration. Head Neck, 21: 239-246, 1999.
3. Berek JS: Ovarian cancer. In: Novak’s Gynecology, 13th edi-
tion, Berek JS (Ed), pp 1245-1321, Lippincott, Williams &
Wilkins, Philadelphia, 2002.
4. Colombo N, Parma G, Zanagnolo V, Insinga A: Manage-
ment of ovarian stromal cell tumors. J Clin Oncol, 25: 2944-
5. Stuart GC, Dawson LM: Update on granulosa cell tumours
of the ovary. Curr Opin Obstet Gynecol,15: 33-37, 2003.
6. Chan JK, Zhang M, Kaleb V, Loizzi V, Benjamin J, Vasilev S,
Osann K, Disaia PJ: Prognostic factors responsible for sur-
vival in sex cord stromal tumors of the ovary - a multivari-
ate analysis. Gynecol Oncol, 961: 204-209, 2005.
7. Gupta N, Rajwanshi A, Srinivasan R, Nijhawan R: Patholo-
gy of supraclavicular lymphadenopathy in Chandigarh,
North India: an audit of 200 cases diagnosed by needle as-
piration. Cytopathology, 17: 94-96, 2006.
8. Gupta RK, Naran S, Lallu S, Fauck R: The diagnostic value
of fine needle aspiration cytology (FNAC) in the assess-
ment of palpable supraclavicular lymph nodes: a study of
218 cases. Cytopathology, 14: 201-207, 2003.
9. Giridharan W, Hughes J, Fenton JE, Jones AS: Lymph node
metastases in the lower neck. Clin Otolaryngol Allied Sci,
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ovary presenting with cervical lymph node involvement: a
report of 3 cases. Am J Surg Pathol, 30: 739-743, 2006.
11. Malpica A, Deavers MT, Gershenson D, Tortolero-Luna G,
Silva EG: Serous tumors involving extra-abdominal/extra-
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of the ovary. Cancer Treat Rev, 34: 1-12, 2008.
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the ovary. Gynecol Oncol, 83: 400-404, 2001.
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metastasis in granulosa cell tumor of the ovary. Cancer, 56:
should be taken into consideration as possible primary
SCSTs are histologically considered to be malignant.
GCT is the most common among these tumors. GCTs
are divided into 2 subgroups based on clinical presenta-
tion and histological characteristics: juvenile and adult
GCTs, the former accounting for only 5% of cases. Im-
munohistochemical staining for inhibin may be of help
in the pathological diagnosis of GCTs, as this character-
istic is very rarely present in other ovarian lesions12.
Different biological behaviors of sex cord tumor have
been described in the literature.There are reported cas-
es of lung, liver, brain, bone-skeleton, diaphragm, ab-
dominal wall, and adrenal gland metastases from SC-
STs13-17. Lymphadenopathy in the neck is an unusual
presentation of malignant neoplasms of the ovary. Only
a few cases have been reported of neck metastases as-
sociated with ovarian malignancies. In a series of 100
autopsies of women who died of ovarian carcinoma,
supraclavicular lymphadenopathy was found in only
4%18. Table 1 gives a summary of case reports for ovari-
an tumors with cervical metastases. Although SCSTs are
generally considered to have low malignant potential
and a favorable prognosis, they may generate distant
metastases. Since distant metastases can occur as late
as 30 years after the initial diagnosis, patients must be
followed up for many years even when the primary tu-
mor is occult4,5. In the present case, supraclavicular
metastasis occurred 4 years after the primary tumor.
Fine-needle aspiration biopsy for cervical lymph
nodes has 92.7% sensitivity and 98.5% specificity for the
primary site. Recent studies using fine-needle aspira-
tion reported the ovary as the primary site in 0.8-9% of
cases of supraclavicular lymph nodes7,8.
Since very few cases of distant metastases from SCSTs
have been reported in the literature, there is no well-de-
fined treatment protocol. The low incidence of SCSTs,
their multiple histological patterns, and their variable
biological behavior limit our knowledge regarding the
optimalmanagement of these tumors. Surgery remains
the most effective treatment for ovarian stromaltumors.
SCSTs are characterized by a long natural history and a
tendency to recur years after the initial diagnosis. Al-
Table 1 - A brief review of the current case reports for ovari-
an tumors with cervical metastases
Author YearNo. of cases Pathology
Malpica et al.11
20015 Serous tumor
Serous borderline tumor
Granulosa cell tumor
Gupta et al.8
Euscher et al.19
Mayadevi et al.20
Verbruggen et al.10
Ismi et al.*
16. Liu K, Layfield LJ, Coogan AC: Cytologic features of pul-
monary metastasis from a granulosa cell tumor diagnosed
by fine-needle aspiration: a case report. Diagn Cytopathol,
16: 341-344, 1997.
17. Williams RJ, Kamel HM, Jilaihawi AN, Prakash D: Metasta-
tic granulosa cell tumour of the diaphragm 15 years after
the primary neoplasm. Eur J Cardiothorac Surg, 19: 516-
18. Dvoretsky PM, Richards KA, Angel C, Rabinowitz L, Stoler
MH, Beecham JB, Bonfiglio TA: Distribution of disease at
autopsy in 100 women with ovarian cancer. Hum Pathol,
19: 57-63, 1988.
19. Euscher ED, Silva EG, Deavers MT, Elishaev E, Gershenson
DM, Malpica A: Serous carcinoma of the ovary, fallopian
tube, or peritoneum presenting as lymphadenopathy. Am J
Surg Pathol, 116: 336-340, 2004.
20. Mayadevi S, Nagarajan S,Van DerVoet JC, Nevin J, Cruick-
shank DJ: Metastatic adenocarcinoma of right supraclavic-
ular fossa – delayed presentation of ovarian primary. J Ob-
stet Gynaecol, 25: 528-529, 2005.
SUPRACLAVICULAR METASTASES FROM AN OVARIAN TUMOR 257