JAZF1–SUZ12 endometrial stromal sarcoma forming subserosal masses with extraordinary uptake of fluorodeoxyglucose on positron emission tomography: a case report

A 69-year-old Japanese postmenopausal (gravida 3, para 3) woman went to her primary physician complaining of urinary incontinence 3 months before admission to our institute. She was suspected of having a uterine mass, which had been growing up in size of 8 cm to 9 cm during prior 2 months. Her medical history was unremarkable. She had no past history of neoplasms and no family history of cancer. Blood testing showed slightly elevated levels of lactate dehydrogenase (LDH) 269 U/L (normal range: 124–222 U/L) and cancer antigen (CA) 125 46 U/mL (cutoff value: 35 U/L). CA 19–9 level was within normal limits. The pelvic examination and transvaginal ultrasonography revealed a fist-sized uterine corpus without abnormalities in other reproductive organs. The cervical cytology was normal. Pelvic magnetic resonance imaging demonstrated a 9 × 8 × 7-cm mass protruding from the right-anterior wall of the uterine corpus that showed heterogenous high intensity on T2-weighted images, and high intensity on diffusion-weighted images (DWI), coexisting with a 4.5 × 3.5-cm mass attached to the right-posterior wall of the uterus and a 6.5 × 4.5-cm intramural mass in the fundus, both demonstrating slightly high intensity on DWI (Figs. 1a-c). On ¹⁸F-FDG-PET, maximum standardized uptake value was 13.28, confined to the tumors located in the uterine right-anterior and right-posterior wall, in sharp contrast to no uptake in the intramural tumor (Fig. 1d). There was no evidence of distant disease. She was radiologically diagnosed with a high-grade uterine sarcoma and concomitant leiomyoma, of which preoperative biopsy was not performed. She underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy and pelvic lymphadenectomy, followed by an uneventful postoperative course. She received no adjuvant therapy, being alive without evidence of recurrence at 14 months after the surgery.

Macroscopically, the removed uterus revealed three separate masses, two of which were located on the uterine right-anterior and right-posterior serosa, respectively, with the remaining mass confined to the fundal myometrium (Fig. 2a). Appearances of the cut surfaces varied by lesion, which were yellow to tan or grayish white coloured, solid or lobulated, accompanied by extensive degeneration and focal hemorrhage in the largest tumor (Fig. 2b). On microscopic examination, the three tumors shared the morphologic feature of proliferating cells having round to ovoid nuclei with a high nuclear-to-cytoplasmic ratio, similar to that of proliferative-phase endometrial stromal cells, with somewhat different cytohistologic features including intercellular edema and fibromyxoid changes in the right-anterior and right-posterior tumors, respectively (Figs. 2c-e). Neither round-cell component nor pleomorphism was identified, and mitoses did not exceed 3 counts per 10 high-power-fields (HPF) anywhere in the three tumors. Vascular permeation was prominent and “worm-like” at the periphery of the fundal tumor, accompanied by focal extrauterine extension of the tumor into the pelvis, swelling 2.0 cm in size (Fig. 2f). Neither lymphatic permeation nor lymph-node metastasis was observed. The uterine cervix and both appendages were not involved by the tumor. The histologic diagnosis was Stage IB low-grade ESS according to the WHO and International Federation of Gynecology and Obstetrics 2014 Classification.

All the three tumors were positive for CD10, Wilms’ tumor 1, estrogen receptor, progesterone receptor, and androgen receptor in most areas, and focally positive for α-smooth muscle actin and h-caldesmon. Cyclin D1 nuclear staining was positive in 50% of neoplastic cells with weak to moderate intensity in the two subserosal tumors whereas the fundal tumor showed < 5% Cyclin D1 positive tumor cells (Figs. 3a-c). Ki-67 labeling indices of the right-anterior, right-posterior, and fundal tumors were 10, 10, and 3%, respectively.

Reverse transcriptase-polymerase chain reaction (RT-PCR) was performed, using formalin-fixed and paraffin-embedded tissues obtained from each uterine tumor and the extrauterine venous extension. Complementary DNA was produced from 1 μg of RNA using an anchored-Oligo (dT)18 primer and Transcriptor First Strand cDNA Synthesis Kit (Roche Diagnostics, Basel, Switzerland). The RT reaction was performed in total 20 μL at 50 °C for 60 min, followed by heating at 85 °C for 5 minutes. The PCR cycling condition was set as follows; an initial denaturing step at 95 °C for 10 min, and 40 cycles at 95 °C for 1 min, 58 or 60 °C for 1 min,72 °C for 30 s. Primers were as follows: JAZF1, forward 5′-AGCAGTGGAAGCCTTACTCC-3′; SUZ12, reverse 5′-GCTATGAGATTCCGAGTTCGAAG-3′; YWHAE, forward 5′ CACTTATCATGCAGTTGTTACGTGAT-3′; FAM22, reverse 5′-GGGCAGAGCCGTGAACAC-3′; β-actin as an internal control, forward 5′- TGGCACCACACCTTCTACAA-3′ and reverse 5′-CCATCACGATGCCAGTGGTA-3′. The same-sized electrophoretic bands indicated amplification of JAZF1–SUZ12 transcripts (Fig. 3d), although YWHAE–FAM22 was not detected in all the tumor components.