Dr. Amirmohsen Jalaeefar studied general medicine at Shahid Beheshti University of Medical Sciences (1997–2004) and then he succeeded to enter general surgery at IRAN University of Medical Sciences (2006–2010). He got his fellowship of surgical oncology from Tehran University of Medical Sciences (2011– 2013). At the beginning of his career, he became assistant professor of surgery at Shahid Beheshti University of Medical Sciences which lasted for 4 years and then he continued as assistant professor of surgery at Tehran University of Medical Sciences, Cancer Institute from 2 years ago until now. His main interest and publication is on the head and neck and the abdominopelvic tumors.
Objective: Granulosa cell tumor (GCT) is a rare entity of ovarian malignancies. Juvenile GCT is considered a malignant tumor with an indolent course and tendency toward late recurrence. However, the association of this tumor and multiple enchondromas has been reported.
Case Presentation: A 17-year-old female with abnormal uterine bleeding was referred to our center. Ultrasonographic evaluation revealed a mass with origin in right ovary. Patient was worked up to undergo salpingo-oophorectomy, she felt a dull pain in her left lower limb. X-ray imaging was indicative for Ollier’s disease at the distal part of femur and proximal part of tibia. Postoperative pathological review was compatible with juvenile granulosa tumor of the right ovary.
Conclusion: This case was the first of its kind that ovarian tumor was contralateral to the side involved by enchondromatosis.
Granulosa cell is a somatic cell in the sex cord of the ovary playing a role in oocyte development [1]. Granulosa cell tumor (GCT) accounts for 5% of all ovarian malignancies and more than 70% of the sex cord stromal tumors [2]. There are two different histological subtypes of GCT, adult (95%) and juvenile type (5%) [3]. GCTs can be distinguished from epithelial ovarian cancer based on the nature of presentation and clinical behavior as GCTs occur in younger patients with features of hyperestrogenism [4]. The metastatic disease is usually identified through histopathological study. The bone metastasis is very rare [5]. Here we represent a case of GCT accompanying with lower limb chondroma.
The patient was a 17-year-old female referred to our clinic (Cancer Institute, Tehran University of Medical Sciences, Tehran, Iran) with primary diagnosis of an abdominal mass. She felt distension of abdomen 3 months prior to the initial visit at our clinic. An abdominopelvic ultrasonography was advised by a private physician which revealed an abdominal mass with probable ovarian origin and ascites.
She complained of early satiety, anorexia, menstruation irregularity and a vague pain in her hip since she felt abdominal distention. On physical examination, a mobile abdominal mass about 20 cm was palpable in the lower abdomen without any tenderness. On hip examination, mild local tenderness was detected on palpation of right iliac wing. There was no other significant sign or symptom in her history or physical examination.
Abdominopelvic magnetic resonance imaging revealed a 160 × 80 mm mass with some necrotic areas in the central part (Fig. 1). It was seen that the mass originated from the right adnexa. A lytic lesion also was unveiled in right iliac wing suspected to be a metastatic bone lesion.
Based on MRI result, ovarian tumor markers and whole-body bone scan was requested. The inhibin level was more than 1000 mcg/dl, and alpha-fetoprotein (AFP), carcino-embryogenic antigen (CEA), cancer antigen 125 (CA125) and human chorionic gonadotropin (HCG) levels were within normal limits. Other laboratory results for blood calcium level and alkaline phosphatase were within normal range. She continued to complain about a dull pain in her left lower limb during diagnostic work up.
The whole-body bone scan was positive for multiple bone lesions in the distal part of the left femur, the proximal part of the left tibia and the right iliac bone reporting possible metastatic lesions.
In order to elucidate the definite diagnosis, the multidisciplinary team (consisted of gynecologists and obstetricians and oncology surgeons) suggested to take biopsies of abdominal mass and iliac bone. Abdominal mass core needle biopsy reported histological features compatible with ovarian sex cord stromal tumor, especially juvenile GCT (IHC was positive for inhibin). Core needle biopsy from iliac lesion showed normal bone trabeculae. In light of bone scan and bone biopsy results, we requested plain bone X-ray from pelvis, skull and her limbs. Multiple lytic bone lesions were found in iliac wing, distal part of the femur and proximal part of the tibia. We asked two independent radiologists to interpret lower limb lesions. It was revealed that these benign bone lesions were mostly compatible with multiple chondroma (Figs. 2, 3, 4).
The patient underwent laparotomy. A midline incision was made, and 5 L of clear ascitic fluid was evacuated. There was no evidence of either peritoneal or visceral metastasis. A 15 × 10 cm mass originating from right ovary was visible which had turned around its pedicle (Fig. 5). After right oophorectomy and omentectomy, a piece of the normal appearing tissue of the left ovary was sent for frozen section analysis. After confirming that the left ovary was histologically normal, a wedge slice of ovarian tissue was sent for tissue freeze to secure future fertility. The postoperative period was uneventful, and she was discharged on the third postoperative day.
The final pathology result confirmed the diagnosis of juvenile GCT. Definite tumor size was measured and found to be 10 × 16 × 11 cm, and the IHC result was positive for CD99 and CD56. Inhibin and calretinin were positive in tumor cells.
Cytologic evaluation of ascitic fluid was negative for malignancy. The omentum and right ovary were tumor free (FIGO stage 1A).
Ollier’s disease (OD) is a nonhereditary skeletal disorder causing multiple enchondromas which may involve tubular bones [6]. Maffucci syndrome (MS) is an association of multiple enchondromatosis with soft tissue hemangiomas [7]. In OD/MS, disruption in cartilage growth leads to abnormal presentation of cartilage in metaphyseal ends of long bones giving rise to multiple endochondromas within the metaphysis [8]. About 25–30% of patients with OD/MS experience malignant transformation and develop chondrosarcomas [8].
Previous studies have reported that the most common ovarian malignant tumor associated with OD and MS is GCT [9]. The first documented case of this association dates back to 1972 by Grenet et al. [9–12]. Table 1 summarizes known cases of the association of OD and MS with juvenile GCT in the literature. It is believed that this association is far beyond coincidence and it points to generalized mesodermal dysplasia, as both juvenile GCT and OD/MS are rare diseases and enchondromatosis has been associated with other congenital dysplastic disease [13, 14].
The majority of juvenile GCTs occurred in the first or second decade of patient’s life [15]. Nearly all reported cases had a symptom of hyperestrogenism as their initial presentation or developed it [2, 9]. Precocious pseudopuberty and menstrual disturbances such as abnormal vaginal bleeding or amenorrhea are the most common ones [1]. It is believed that the association of OD/MS and juvenile GCT does not influence clinical course of the GCT and it is the same as cases without this association [4]. Our patient complained of menstrual irregularity, but her puberty stages were normal. Most reports on association of OD and GCT indicate that enchondromatosis happens on the same side that ovarian neoplasm occurs [12, 13, 16, 17]. Although Pounder et al. [18] reported bilateral involvement, these tumors were not synchronous and happened with 7-year interval. To our knowledge, our case is the first example of OD occurring in contralateral side to juvenile GCT.
The International Federation of Gynecology and Obstetrics have provided detailed staging of ovarian tumors [19]. Most cases of juvenile GCT happen in early stages leading to good prognosis. However, it is necessary to closely follow the patients as GCT has an indolent course for possible recurrence especially in the first or second decade, and also it might transform to chondrosarcoma. The prognosis of OD/MS with juvenile GCT depends on the stage of juvenile GCT. The mortality rate for stage Ia or Ib is 2.5%, whereas for stage Ic it rises to 38% [1]. In this regard, current guidelines suggest ipsilateral salpingo-oophorectomy without subsequent chemotherapy [5, 20].
Conflict of interest All authors declare that there is no conflict of interest to disclose.
Human Participants and/or Animals All parts of Declaration of Helsinki have been applied.
Informed consent The patient gave us written consent of her inclusion in the study.
