We retrospectively analyzed the existing medical records of patients admitted to Oita University Hospital and Saitama Medical University International Medical Center between April 2014 and March 2023. We searched the medical records for cases that met both the criteria of ‘ovarian cancer’ and ‘bone marrow metastasis.’ One case was identified from each institution. The Institutional Review Board of the Ethics Committee of each institution approved this study (approval Code: 2586 and 16-257, approval Date: August 4, 2023 and September 5, 2018 respectively). Data were extracted from obstetric and gynecological records of patients diagnosed with BMM of ovarian cancer. This study adhered to the guidelines of the Declaration of Helsinki and was performed in conjunction with the prevailing ethical regulations. All patients provided written informed consent for publication. Patient information, including the age at diagnosis, chief complaint, history of pregnancy and delivery, past medical history, family history, clinical courses, treatment methods, blood tests, clinical imaging, pathological findings, and outcome, was collected.

The PubMed^® database was searched from inception until June 2024. The keywords used were ‘ovarian cancer,’ ‘ovarian carcinoma,’ ‘bone marrow metastasis,’ ‘bone marrow carcinomatosis,’ and ‘disseminated carcinomatosis of bone marrow.’ Junya Nakajima and Mitsutake Yano screened titles, abstracts, and full-text articles. Articles/case reports discussing BMM of ovarian cancer were included. The article also needed to be available in English, and either be open-access or available through the library of Oita University or Saitama Medical University International Medical Center. Articles with incomplete data, articles for which original data could not be obtained, conference abstracts, or animal/in vitro studies were excluded. Patient information, including the number of cases, age at diagnosis, chief complaint, clinical courses, treatment methods, blood tests, clinical imaging, pathological findings, and outcome, was collected.

We identified two and six cases of BMM of ovarian cancer in our institutions and the literature review, respectively. Table I summarizes these cases (2-5). Eight cases have been reported; however, detailed pieces of information, such as blood tests, imaging tests, symptoms, and clinical courses, were only described in the present two cases. The patients' ages ranged from 37 to 71 years (median 51 years), while tumor histology was described in five of the eight cases. Notably, all three previous cases involved rare histological types (small cell carcinoma, carcinosarcoma, and mucinous carcinoid) of ovarian cancer, and only the present two cases involved the common histological types (high-grade serous carcinoma and clear cell carcinoma). Two of the three available cases had a history of chemotherapy; however, only case 1 received platinum-based chemotherapy and maintenance chemotherapy with poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitors, which are the standard treatments for epithelial ovarian cancer. Detailed information regarding two cases in our institutes is provided below.

A 64-year-old woman visited Oita University Hospital for evaluation of a pelvic mass. A summary of the patient's clinical course is illustrated in Fig. 1. The patient experienced frequent urination and constipation. Contrast-enhanced magnetic resonance imaging (MRI) and computed tomography (CT) revealed an 80 mm-sized pelvic tumor with peritoneal dissemination, enlarged pelvic lymph nodes, and ascites (Fig. 2A). The serum cancer antigen 125 (CA125) level was elevated (7,198 U/ml). Tumor biopsy revealed a high-grade serous carcinoma. The patient was diagnosed with stage IIIC ovarian cancer (cT3cN1M0). Debulking surgery (including hysterectomy and bilateral salpingo-oophorectomy), with each of three courses of neoadjuvant and adjuvant chemotherapy (paclitaxel: 80 mg/m² [weekly]; carboplatin: area under the blood concentration-time curve [AUC], 6 [tri-weekly]), was performed. All tumors were resected. Postoperative histological examination revealed stage IIIC ovarian cancer (ypT3cN1M0) (Fig. 2B). An isolated splenic metastasis was detected 43 months after the final round of chemotherapy. The patient subsequently underwent abdominal splenectomy and six courses of adjuvant chemotherapy (paclitaxel: 180 mg/m²; carboplatin: AUC 6, tri-weekly). A complete response was obtained, and olaparib was initiated. Precisely 19 months after initiation, olaparib was withdrawn because of Common Terminology Criteria for Adverse Events (CTCAE) grade 3 anemia. After 1 month, CTCAE grade 3 anemia and thrombocytopenia were diagnosed, and a blood transfusion was performed. This point was retrospectively considered to be the onset of BMM based on persistent cytopenia despite olaparib withdrawal and elevated CA125 levels. Exactly 1 month later, severe anemia and thrombocytopenia continued, and she had a fever of 38.7˚C. Her blood tests revealed the following levels: C-reactive protein (CRP), 11.11 mg/dl; white blood cell (WBC), 3.72x10³ cells/µl; hemoglobin, 6.1 g/dl; platelet, 1.7x10³ cells/µl; aspartate aminotransferase (AST), 74.6 U/l; lactate dehydrogenase (LDH), 2,712 U/l; and alkaline phosphatase (ALP), 81 U/l. The CA125 level was elevated to 117 U/ml. Contrast-enhanced CT revealed no obvious recurrence or focus of infection. Bone marrow biopsy revealed BMM/carcinomatosis of ovarian cancer (Fig. 2C). Immunohistochemically, the BMM tumor cells were positive for p53 and negative for AE1/AE3. The patient died owing to BMM of ovarian cancer and DIC 4 weeks following BMM onset and 1 week after admission/serum LDH elevation.

A 51-year-old woman was admitted to Saitama Medical University International Medical Center owing to abdominal bloating, severe anemia, and elevated CA125 levels. Contrast-enhanced MRI and CT revealed bilateral ovarian tumors (Fig. 2D) and multiple bone masses (Fig. 2E). No peritoneal dissemination or lymph node metastasis were observed. Her blood tests revealed the following levels: CRP, 15.28 mg/dl; WBC, 12.11x10³ cells/µl; hemoglobin, 3.3 g/dl; platelet, 426x10³ cells/µl; AST, 22 U/l; LDH, 339 U/l; and ALP, 526 U/l. The CA125 level was elevated to 3,306 U/ml. The patient underwent abdominal total hysterectomy, bilateral salpingo-oophorectomy, and omentectomy. Intraoperative findings revealed no peritoneal dissemination or ascites. Her peritoneal cytology results were negative for malignancy. On postoperative day 5, the patient experienced hemorrhagic shock caused by bleeding from the internal iliac artery, for which hemostasis was achieved using interventional radiology. Pathologically, the right and left ovarian tumors were clear cell carcinoma (Fig. 2F) and endometriotic cysts, respectively. On postoperative day 21, bone marrow biopsy revealed carcinomatous necrosis with immunohistochemical AE1/AE3 positivity (Fig. 2G and H). Subsequent positron emission tomography (PET)-CT confirmed the presence of multiple bone metastases without other metastases. The patient was diagnosed with stage IVB ovarian cancer (pT1aN0M1b, clear cell carcinoma) and BMM/carcinomatosis. She did not receive systemic chemotherapy because of her poor general health. She died of BMM and DIC 50 days postoperatively.