Ovarian tumors are rarely diagnosed as steroid cell tumors; these account for less than 0.1% of all ovarian tumors. Steroid cell tumors of the ovary have a diverse cellular origin; they are a group of ovarian neoplasms with morphologic similarities that, in the past, were termed as lipid or lipoid cell tumors. These tumors are made of cells that resemble steroid hormone secreting cells, but some cases show scarce or no lipid components and some tumors have a tendency to secrete various steroid hormones with specific clinical presentations. For these reasons, Hayes and Scully [2
] proposed the term steroid cell tumor, which was accepted by World Health Organization in 1999.
Steroid cell tumors, NOS are found in almost any age group, from premenarchal girls to postmenopausal women, with an average age at diagnosis of 43 years [2
]. The clinical presentation may take many forms, including abdominal pain, distention, and bloating. However, the more noticeable presentations are those associated with hormonal activity. Steroid cell tumors secreting steroid hormones are prevalent, mostly secreting testosterone in 50% of steroid cell tumors, NOS [3
]. About 8% to 23% of steroid cell tumors, NOS, show signs of estrogen secretions, and cortisol secretion may be diagnosed in 6% to 10% of cases [2,5
]. A minority of 10% to 15% of patients with steroid cell tumor, NOS have no symptoms of increased steroid hormone production [3
]. In this case, the apparent absence of androgenic manifestations is an unusual finding.
The size of steroid cell tumors, NOS range from under 1 cm to over 45 cm, and the average size at diagnosis is known as 8.4 cm [2
]. These tumors are mostly unilateral, with 6% bilateral, and are typically well circumscribed solid tumors in 89% of cases, generally yellow in color, and in some cases lobulated [2,5
]. Necrosis and hemorrhage may be found, and only one tumor of the 61 cases studied by Hayes and Scully was described as almost completely cystic [2,5
]. An extensive review of case reports in the PubMed database from 1979 until the present revealed only 5 cases that were mainly cystic tumors. No cases have been illustrated, to our knowledge, with inner septa and extensive adhesion to surrounding structures. In our patient, the tumor was a 9 cm sized overall cystic mass with septations and a small solid portion, with tight adhesions to the bladder and bowels (so much so that reparative procedures were necessary after extraction of the mass).
The majority of steroid cell tumors have benign or low-grade behavior. These tumors are found comparatively early due to endocrine activity, and show low rates of recurrence and metastasis [2,5
]. About 25% to 43% are reported clinically malignant [2,5
], and in such cases 44% to 83% show symptoms of hormone impairment such as virilization, and 17% are associated with Cushing's syndrome due to cortisol increase [2
]. Hayes and Scully [2
] detailed five microscopic findings that are highly associated with malignancy: 1) the presence of two or more mitotic figures per 10 HPF in 92%, 2) necrosis in 86%, 3) a diameter of 7 cm or greater in 78%, 4) hemorrhage in 77%, and 5) grade 2 or 3 nuclear atypia in 64% of cases [2
]. In our case, as the size of the mass was large (9 cm) and 5 mitotic figures per 10 HPF were observed, malignancy was a possibility, but as no foci of necrosis or hemorrhage, no nuclear atypia, and no signs of invasion or metastasis were evident, we considered the tumor to be benign, and the patient has shown no signs of recurrence during 21 months of follow-up.
Immunohistochemistry may be utilized in diagnosis, and generally inhibin is used. Inhibin is present in ovarian granulosa and lutein cells, where it suppresses the production of pituitary gonadotropins [6
]. Steroid cell tumors, NOS are positive for inhibin and vimentin in 75%, 7% are positive for S-100 protein, and they are negative for chromogranin A [7
]. Calretinin, a calcium-binding protein discovered in mesothelial cells, is also present in the ovary and testis, and is expressed by sex-cord stromal tumors [6
]. Deavers et al. [6
] found that the extent of staining for inhibin ranged from under 5% to over 90%, and 60% to over 90% for calretinin, in 6 cases of steroid cell tumor, NOS; all cases were positive for inhibin and calretinin. CD99 is another marker expressed by sex-cord stromal tumors and it reacts with normal granulosa and Sertoli cells, and it showed membranous staining in one of the previous 6 cases [6
]. Our case was positive for inhibin, calretinin, and vimentin, moderately positive for CD99, and negative for S-100 protein and chromogranin A, with a diagnosis of steroid cell tumor, NOS.
No specific tumor markers or imaging techniques are known for preoperative diagnosis of steroid cell tumors. Tumor markers such as CA-125 and α-fetoprotein, etc., are generally normal and the literature does not indicate if elevated levels signify malignant potential. This case demonstrated a normal level of CA-125, and although CA-19-9 was temporarily mildly elevated, this is considered to result from the patient's underlying liver cirrhosis. Imaging before surgery may be checked for ovarian or adrenal masses, and vaginal or abdominal ultrasound may help to identify ovarian mass characteristics. Wang et al. [8
] found preoperative magnetic resonance imaging to be an effective means for staging and gadolinium-diethylene-triamine-pentaacetic acid enhancement to be helpful for locating metastasis within the pelvic cavity. In another study, Wang et al. [9
] reported whole-body positron emission tomography with [11C]acetate to aid in the diagnosis of steroid cell tumors that were secreting testosterone. Most recently, Sakamoto et al. [10
] proposed chemical shift magnetic resonance imaging as a technique for diagnosis by observing the cytoplasmic lipid content of steroid cell tumors.
No definitive treatment is established for steroid cell tumors, NOS, due to their rarity, but the tumors are considered to be sex cord-stromal tumors and the primary treatment is surgery. Only 6% are bilateral, so a young woman desiring future childbearing with a low stage tumor may undergo unilateral salpingo-oophorectomy, with regular monitoring of any preoperatively increased hormones. An older woman with a low stage tumor and no desire for parity may have a total hysterectomy with bilateral salpingo-oophorectomy. A high stage tumor should undergo size reduction and adjuvant chemotherapy or radiation therapy should be considered [2
]. However, as symptoms lead to early diagnosis and as recurrence or metastasis is rare, the research on adjuvant therapy is insufficient and many are skeptical. If preoperatively increased testosterone does not change after surgery, gonadotropin releasing hormone agonists may be utilized [11
]. As steroid cell tumors, NOS are rare, their staging and prognosis is unclear, but Hayes and Scully [2
] analyzed 63 cases as 88% stage 1, 6.8% stage 2, 12% stage 3, and 1.7% stage 4 [2
]. Cases with a higher stage, larger size, gross necrosis, or hemorrhage were found to have higher malignant potential with worse prognosis [2
]. Recurrence or metastasis were also associated with worse prognosis due to insufficient research on additional treatment options.
Some observations indicate that the incidence of ovarian tumors rises after hysterectomy. The overall incidence of ovarian pathologic findings requiring repeat operation after hysterectomy for benign conditions has been reported as 3.8% [4
]. Only 3 cases of steroid cell tumor diagnosed after a previous hysterectomy have been described, and our case is the fourth [12-14
The almost completely cystic characteristic of our case was unusual for a steroid cell tumor, NOS, which are usually solid tumors, and this case shows that even in an apparently benign, mostly cystic, ovarian tumor, a rare steroid cell tumor with undetermined behavior may be diagnosed. Careful clinical assessment should be carried out when evaluating ovarian tumors. In our case, the patient showed no signs of recurrence or metastasis, which are considered to be malignant behavior. The most important factor to be determined in steroid cell tumors of the ovary is whether the tumor has malignant features. Steroid cell tumors, NOS are clinically malignant in 25% to 43% of cases, and pathologically benign steroid cell tumors are known to behave in a clinically malignant fashion. Therefore, careful follow-up after surgery is imperative even in those cases that do not have clinical or pathological evidence of malignancy.
We report a patient with a history of hysterectomy, with an incidentally found, asymptomatic, predominantly cystic tumor with internal septa and an inner solid portion, which was diagnosed as steroid cell tumor, NOS. The patient has had no signs of recurrence for 21 months after surgery. We also provide a brief review of the existing literature.