Background Low-grade endometrial stromal sarcoma (ESS) is rare mesenchymal neoplasm, recently specified as harboring JAZF1–SUZ12 rearrangement. Typical JAZF1–SUZ12 ESS is slow growing, in which high uptake of fluorodeoxyglucose (FDG) on positron emission tomography (PET) and subserosal masses are quite unusual. Case presentation A 69-year-old Japanese woman complained of urinary incontinence. Pelvic magnetic resonance imaging showed uterine lesions composed of (1) a 9 × 8 × 7-cm mass protruding from the right-anterior wall, (2) a 4.5-cm mass attached to the right-posterior wall, and (3) a 6.5-cm intramural mass in the fundus. FDG-PET demonstrated maximum standardized uptake value of 13.28 confined to the two subserosal masses (1 & 2) in contrast to no uptake of the intramural mass (3). She was diagnosed with a high-grade uterine sarcoma concomitant with leiomyomas and underwent total hysterectomy with bilateral salpingo-oophorectomy and pelvic lymphadenectomy. The removed uterus had three tumors—two in the right-anterior and right-posterior subserosa, respectively, and the remaining in the fundal myometrium. Microscopically, the three tumors shared morphologic features characterized by neoplastic cells similar to proliferative-phase endometrial stromal cells, in which neither round-cell component, pleomorphism, nor high mitotic activity was recognized. Nuclear cyclin D1 immunostaining was identified 50% of neoplastic cells in the two subserosal tumors (1 &2) whereas < 1% positive cells in the intramural component (3). Reverse transcriptase-polymerase chain reaction showed the same-sized electrophoretic bands indicating JAZF1–SUZ12 gene fusion shared by the three uterine tumors and a focal tumor extension into the extrauterine vein. The patient is alive without evidence of recurrence at 14 months after surgery. Conclusions Pathologists and clinicians should not exclude the possibility of JAZF1–SUZ12 ESS even when uterine subserosal masses demonstrate extraordinary FDG uptake on PET. Molecular analysis is helpful for diagnostic confirmation of JAZF1–SUZ12 ESS with a complex growth pattern.

BackgroundPagetoid spread of urothelial carcinoma (UC) to the lower genital tract is quite a rare and diagnostically challenging condition. Pagetoid urothelial intraepithelial neoplasia extending to the vagina is difficult to diagnose, especially in remote recurrences without symptomatic or macroscopic lesions typical to Paget disease. However, its identification by cervical screening cytology is important because UC is often characterized by a long history of relapse.Case presentationA 68-year-old Japanese postmenopausal woman developed brown vaginal discharge after radical cystectomy for bladder cancer (high-grade UC, pT2a pN0 cM0 [Union for International Cancer Control, 8th edition]) concomitant with focal in-situ UC in the urethra. She had a history of left renal pelvis UC, which was surgically removed 9 months before the radical cystectomy. Gynecologic examination of the lower genital tract was unremarkable although cervical screening cytology demonstrated severely atypical cells with pleomorphism repeatedly. Cervical colposcopy and diagnostic conization revealed no cervical neoplasm. In retrospect, immunocytochemical p16/Ki-67 dual staining for the previous cervical screening was negative for p16 labeling, and the neoplastic cells were positive for cytokeratins 7 and 20, p63, and GATA binding protein 3. No high-risk human papillomavirus genotype was identified by an automated DNA chip system using liquid-based cytology samples. Eleven months post-cystectomy, punch biopsy of the vulva and vagina confirmed intraepithelial UC in the juxtaposed squamous epithelium with pagetoid spread demonstrating positivity for specific urothelial markers: uroplakins II and III and thrombomodulin. Concurrent invasive malignancy was ruled out, and CO2 laser vaporization of the vulvar and vaginal lesion was performed. The patient remained alive without evidence of invasive malignancy for 14 months after the radical cystectomy for bladder cancer.ConclusionsTo detect recurrent pagetoid urothelial intraepithelial neoplasia with pagetoid spread in the lower genital tract, pathologists should recognize the history of prior UC with special attention to absence of p16 labeling in cervical cytology as a pointer to the diagnosis of urothelial cancer. Using further biopsy and immunohistochemical confirmation of UC relapse, investigation to rule out invasive malignancies and careful follow-up throughout the patient’s lifetime is recommended.

BackgroundOvarian serous borderline tumor/atypical proliferative serous tumor (SBT/APST) is characterized by presenting at an early stage and much longer survival than high-grade serous carcinoma. Given that the prognosis of ovarian SBT/APST with no invasive features is excellent, remote relapse after surgery can pose a diagnostic pitfall. Bone metastasis as transformed low-grade carcinoma is an extremely rare initial presentation of recurrence in patients whose primary tumor was confined to the ovaries.Case presentationA 55-year-old Japanese woman who had undergone surgery for a right ovarian tumor 13 years previously presented with right-lateral chest pain and neurologic abnormalities in the lower limbs. Computed tomography (CT) scan and magnetic resonance imaging revealed an irregular mass in the right arch of the 12th thoracic vertebra, extending through the intervertebral foramen and into surrounding soft tissue, the maximum diameter of the whole mass being 78 mm. Pathological examination of a CT-guided needle biopsy of the paraspinal lesion demonstrated papillary cell clusters with blunt nuclear atypia and psammomatous calcification that were positive for PAX8, estrogen receptor, and WT1, but negative for thyroglobulin on immunohistochemical testing, and of a P53 non-mutational pattern. On clinicopathologic review, the previous 13- × 11- × 9-cm ovarian tumor was an intracystic and exophytic papillary growth without surface involvement; it had ruptured intraoperatively. Microscopically there was serous epithelium with minimal cytologic atypia proliferating in hierarchical branches with no invasive foci or micropapillary components. The tumor was confined to the right ovary with no peritoneal implants. Neither primary nor metastatic tumor harbored KRAS/BRAF mutations according to polymerase chain reaction using formalin-fixed paraffin-embedded tissues. We concluded that, after a 13-year disease-free interval, the paraspinal lesion was bone metastasis of low-grade carcinoma originating from the ovarian SBT/APST. The patient received radiotherapy for the paraspinal lesion followed by administration of paclitaxel and carboplatin plus bevacizumab and remains alive 168 months after the initial surgery.ConclusionsPathologists and radiologists should not exclude late recurrence of ovarian SBT/APST when bone metastases are suspected, even when neither peritoneal nor lymph node involvement are detected. Long-term surveillance of women with ovarian serous tumors with no invasive features is recommended.

BackgroundCD5-positive diffuse large B-cell lymphoma (DLBCL) and intravascular large B-cell lymphoma (IVL) are recognized as rare subsets of large B-cell lymphoma with poor prognosis. These two categories have similar clinicopathological features suggesting that they might overlap.Case presentationWe present a case of a 72-year-old man with submental tumors. Positron emission tomography/computed tomography (PET/CT) showed tumors in the nasal and paranasal region and multiple submental and jugular swollen lymph nodes with abnormal uptake of 18F-fluorodeoxyglucose (FDG). Histology of biopsy from nasal tumors showed diffuse infiltration of large lymphoid cells, which showed positive expressions for CD20, CD79a, CD5 and negative for CD3 on immunohistochemistry. Thus, a CD5-positive DLBCL was diagnosed. After administration of 8 cycles of R-THPCOP (rituximab, pirarubicin, cyclophosphamide, vincristine and prednisolone), complete remission was achieved. Eight months after the first chemotherapy dose, local recurrence occurred. After salvage chemotherapy, nasal and paranasal tumors and lymph node swelling disappeared on PET/CT images, although the patient suffered from respiratory disturbance. A random skin biopsy revealed IVL, which was consistent with intravascular recurrence of CD5-positive DLBCL. Bone marrow smears showed hemophagocytosis.ConclusionWe present a rare case of primary CD5-positive DLBCL that relapsed as pure IVL after chemotherapy. Our case suggests that CD5-positive DLBCL is closely related to IVL.

Introduction: Pulmonary tumor thrombotic microangiopathy (PTTM) is a rare cancer-associated respiratory complication characterized by widespread tumor cell emboli in small arteries and arterioles of the lung. Breast cancer is the second most common cancer causing PTTM. The pathogenesis and molecular background of PTTM have not been clarified. Here we present a case of breast cancer that experienced early onset of liver metastasis after surgical resection of the primary tumor and rapid progression leading to death due to severe respiratory distress. Autopsy was performed and it revealed that the main cause of her death was PTTM. Comprehensive next generation sequencing (NGS) analysis of the tissue obtained serially during the clinical course was performed. Case Presentation: A 48-year-old woman was diagnosed with invasive ductal carcinoma of the left breast, which was ER positive, PgR negative, and HER2 negative. FEC followed by docetaxel was administered as preoperative chemotherapy. Her tumor dramatically shrunk with chemotherapy and left partial mastectomy with left axillary lymph node dissection was performed. Histopathological analysis of the resected breast tissue revealed that there were a lot of residual cancer cells, which were ER negative, PgR negative, HER2 negative, and the result indicated that response to preoperative chemotherapy was insufficient. Additional two courses of FEC therapy were performed. Postoperative radiation therapy including the left supraclavicular lymph node area was given and adjuvant endocrine therapy with anastrozole started at the same time. At 3 months of anastrozole administration, she presented hepatic dysfunction and abnormal CT findings in the liver. Liver biopsy revealed multiple liver metastasis of breast cancer. Unresponsive to weekly paclitaxel and bevacizumab, she developed rapid respiratory failure leading to her death in two weeks. Postmortem microscopic analysis revealed an intimal fibrocellular proliferation in the pulmonary arterioles regardless of microscopic tumor emboli and extensive sinusoidal metastasis of the whole liver. NGS Analysis: We analyzed four specimens, breast cancer biopsy specimen at diagnosis, surgical resection specimen, liver needle biopsy specimen, and liver specimen obtained at autopsy, with the Ion AmpliSeq Comprehensive Cancer Panel (Thermo Fisher). The results were compared with NGS analysis of her normal lung tissue to exclude single nucleotide polymorphisms. Deep sequencing revealed that only TP53 R213* was detected as an oncogenic mutation in all four specimens. There were no mutations associated with the development of liver metastasis and her death. Comparison of the samples obtained between before and after liver metastasis revealed that STK11 loss and IKBKE amplification were harbored only in the specimens after liver metastasis. RNA sequencing analysis with the samples of initial biopsy and liver biopsy showed that the RNA expression associated with apoptosis and adhesion molecules was strongly suppressed in the liver sample. Conclusion: STK11 encodes a serine/threonine kinase, which organizes cell polarity and inhibits tumor growth. In the present patient, STK11 loss had occurred during the treatment and could induce rapid progression of her disease and PTTM. Citation Format: Fumie Fujisawa, Kei Kunimasa, Rieko Kano, Hiroki Kusama, Minako Nishio, Saki Matsui, Tetsuhiro Yoshinami, Nobuyoshi Kittaka, Shigenori Nagata, Toshinari Yagi, Takahiro Nakayama, Yasuhiro Tamaki, Fumio Imamura. SKT11 loss drives rapid cancer progression and fatal pulmonary tumor thrombotic microangiopathy (PTTM) in a breast cancer patient: A case report [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS16-31.