Open Access

Cancer of unknown primary histologically, genetically and spatially diagnosed as left ovary‑derived cancer: A case report

  • Authors:
    • Harunori Honjoh
    • Ayumi Taguchi
    • Hirofumi Rokutan
    • Ayako Mori
    • Takahiro Ando
    • Akira Nishijima
    • Satoko Eguchi
    • Yuichiro Miyamoto
    • Kenbun Sone
    • Mayuyo Uchino‑Mori
    • Yutaka Osuga
  • View Affiliations

  • Published online on: October 19, 2023
  • Article Number: 522
  • Copyright: © Honjoh et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Cancer of unknown primary (CUP) is a heterogeneous syndrome of metastatic cancer in which the primary site cannot be determined even after a standard and comprehensive search. The present report describes a case in which the spatial distribution of the lymph node metastases contributed to the identification of the primary site. While the standard workup did not identify the primary tumor, genomic profiling analysis was useful in therapeutic management. A 68‑year‑old woman presented with a cancerous pleural effusion (adenocarcinoma). The primary site could not be identified, and the pleural effusion resolved spontaneously. After 11 months, the patient had elevated Krebs von den Lungen‑6 and cancer antigen 125 levels, and multiple enlarged lymph nodes. Pathological diagnosis based on a biopsy sample of the para‑aortic lymph nodes indicated that the tumor was a high‑grade serous carcinoma of possible gynecological organ origin. The patient underwent surgery, including hysterectomy, bisalpingo‑oophorectomy and lymph node dissection. Although there were no primary sites in the gynecological organs, marked lymphovascular invasion was found around the left ovary, suggesting a left ovary‑derived tumor. Genetic testing revealed a high loss of heterozygosity score and high tumor mutational burden (TMB). The patient received paclitaxel and carboplatin therapy followed by a poly ADP‑ribose polymerase inhibitor as regimens for ovarian cancer and achieved complete remission. The unique course of the disappearance of the effusion and the absence of tumor in the adnexa might be associated with the high immunogenicity of the tumor characterized by the high TMB. This case may provide insights into the pathogenesis of CUP.


Cancer of unknown primary (CUP) is a heterogeneous syndrome of metastatic cancers in which the primary site cannot be determined after a standard and comprehensive search, and accounts for 1–5% of all newly diagnosed malignancies (1,2).

CUP falls into either the clinicopathologically ‘favorable’ (~15% of cases) or ‘unfavorable’ (~85% of cases) subgroups (35). The former includes adenocarcinoma of the axillary lymph nodes, papillary serous carcinoma of the peritoneum (redefined as peritoneal cancer), squamous cell carcinoma of the cervical lymph nodes and extragonadal germ cell tumors in young men, which are derived from the middle of the body (4). For these patients, specific therapeutic management can be provided, and satisfactory local control and prolonged survival can be expected, with a median survival time of >24 months (6). On the other hand, the unfavorable subset (majority of patients) includes patients with adenocarcinoma metastasis to the liver or other organs, poorly differentiated carcinoma and squamous cell carcinoma of the abdominal cavity (1). These patients are usually treated with empiric chemotherapies based on platinum and taxanes (7) but are generally not chemosensitive and have a poor prognosis, with a median survival time of 5–8 months (4,8).

Delayed initiation of treatment and a tendency to choose empiric chemotherapy are associated with a poor prognosis (4). Therefore, a thorough workup at the time of diagnosis is important in CUP. The distribution and histology of the cancer are important for estimating the primary site. In addition to image-based and immunohistochemical examinations, the cancer genomic profiling (CGP) test has been used to estimate primary sites and identify potential targets for personalized therapies (9,10). Several studies using next-generation sequencing have demonstrated that molecular profiling for CUP is useful for predicting the tissue of origin (9,1114). However, to the best of our knowledge, it has not been determined whether genomic profiling in CUP can help in providing tissue-specific therapies, including targeted therapies, to improve survival. A prospective randomized phase II trial (CUPISCO trial; NCT03498521) is currently underway to investigate the efficacy of CGP in CUPs; however, there are issues, such as insufficient sample volume and cases of misdiagnosis (15,16).

In the present study, a case of CUP is reported in which genomic profiling and lesion distribution were used to infer the primary organs of cancer and to determine a suitable therapeutic strategy.

Case report

A 68-year-old woman, gravida 1 para 1, who had a history of allergic dermatitis for 2 years and had been taking prednisone irregularly, presented to their primary care physician (Yokohama, Japan) in August 2020 with dyspnea on exertion. Right pleural effusion was observed, and 1,600 ml pleural fluid was aspirated by puncture. Papanicolaou staining was performed on the pleural fluid as previously described (17), and the cytological examination revealed Class V adenocarcinoma (Fig. 1A) according to the Papanicolaou classification (18). Upper and lower gastrointestinal endoscopy and gynecological examination were performed but the primary tumor was not identified. In October 2020, the patient was referred to the Department of Respiratory Medicine, Graduate School of Medicine, The University of Tokyo (Tokyo, Japan). By then, the pleural effusion had resolved spontaneously. Positron emission tomography-computed tomography (PET-CT) revealed mild fluorodeoxyglucose accumulation in the left predominant para-aortic and left internal iliac lymph nodes; however, this was considered to be a reactive change. At 11 months after the initial visit, the Krebs von den Lungen-6 level measured using chemiluminescent enzyme immunoassay (CLEIA) was elevated (1,243 U/ml; normal range, 0–464 U/ml), and the patient was referred back to the hospital for a close examination of the primary site. PET-CT revealed abnormal accumulation in the right axillary lymph node with a maximum standardized uptake value (SUV) of 3.8, and further accumulation in the peripancreatic, para-aortic, mesenteric, sacral and bilateral external iliac lymph nodes with a maximum SUV of 7.2. All lymph node accumulations were considered to indicate metastatic lymph nodes (Fig. 1B).

Due to elevated cancer antigen 125 (CA125) levels (309 U/ml; normal range, 0–35 U/ml) measured using CLEIA and the distribution of the metastatic lymph nodes, gynecological cancer was suspected; however, pelvic magnetic resonance imaging showed no obvious primary tumor and multiple uterine fibroids (Fig. 1C). The cervical and endometrial cytologies were negative. Fine-needle aspiration cytology of the right axillary lymph node revealed metastatic adenocarcinoma (data not shown). For histological diagnosis, a laparoscopic para-aortic lymph node biopsy was performed. Hematoxylin-and-eosin (H&E)-stained slides were made from formalin-fixed paraffin-embedded (FFPE) blocks as previously described (17). Immunohistochemical staining was performed using the Ventana BenchMark XT automated staining system (Roche Diagnostics) according to the manufacturer's protocol, as previously described (19). The primary antibodies used were as follows: Cytokeratin 7 (cat. no. 790-4462; clone SP52; Roche Diagnostics), estrogen receptor (EP1, Envision FLEX-ER, Dako; Agilent Technologies, Inc.), paired box 8 (clone 10336-1-AP; Proteintech Group, Inc.), p53 (clone DO-7; Roche Diagnostics), Wilm's tumor 1 (clone 6F-H2; Dako; Agilent Technologies, Inc.), GATA binding protein 3 (clone L50-823; Biocare Medical, LLC), cytokeratin 20 (clone SP33; Roche Diagnostics) and D2-40 (clone D2-40; Dako; Agilent Technologies, Inc.). All the cytopathological, histological and immunohistochemical images were examined and captured using a light microscope (BX51; Olympus Corporation). The tumor was diffusely positive for cytokeratin 7, estrogen receptor, paired box 8, p53 and Wilms tumor 1, whereas it was negative for GATA binding protein 3 and cytokeratin 20 (Fig. 2A). The histological and immunohistochemical diagnosis was of a high-grade serous carcinoma (HGSC) possibly derived from the gynecological organs, based on the WHO Classification (20).

Figure 2.

Distribution and pathological diagnosis of cancer of unknown primary. (A) Pathological examination of para-aortic lymph node biopsy. The upper left image shows H&E staining (magnification, ×40). The upper right image is a magnified image of the area enclosed by the yellow square in the upper left image (magnification, ×100). Sheets of cancer cells with necrotic foci were observed. The cancer cells had enlarged and irregularly shaped nuclei with distinct nucleoli. The lower images show immunohistochemical analysis of CK7, CK20, ER, PAX8, p53 and WT1 (all magnification, ×200). (B) Macroscopic image of surgically removed uterus and bilateral adnexa. The unit on the scale is 1 mm. (C) Distribution of metastatic lymph nodes determined by pathological diagnosis of surgically removed lymph nodes and CT, MRI and PET-CT images. Metastatic lymph nodes are shown in red. This figure was created by the author using BioRender with permission to reproduce images from Reprinted from ‘Circulatory system (female, lymphatic)’, by (2023). Retrieved from (D) Pathological examination of the left ovary. Adenocarcinoma was present in lymphatic vessels. The morphology of tumor clusters was similar to the clusters observed in the pleural fluid cytology specimens. H&E staining (left) and D2-40 (right) magnification, ×100; WT1 (center) magnification, ×200. CK7, cytokeratin 7; CK20, cytokeratin 20; D2-40, podoplanin; ER, estrogen receptor; PAX8, paired box 8; WT1, Wilms tumor 1; PET-CT, positron emission tomography-computed tomography.

Based on the distribution of the tumors, high CA125 levels, histology and immunostaining results, HGSC of the ovary or fallopian tubes was suspected to be the primary carcinoma. For the purpose of diagnosis and tumor debulking, a total abdominal hysterectomy, bilateral salpingo-oophorectomy, pelvic and para-aortic lymphadenectomy, and partial omentectomy were performed (Fig. 2B). Pathological examination of the surgical specimen, including histological assessment of H&E-stained slides of FFPE tissues, revealed that there were no primary tumors in the parenchyma of the ovaries or fallopian tubes, and also no peritoneal dissemination, with negative peritoneal washing cytology, or serous tubal intraepithelial carcinoma; however, there were multiple metastatic adenocarcinomas in para-aortic and pelvic lymph nodes. Although some lymph node metastases were present on both sides, including the para-aortic, sacral and external iliac lymph node metastases, some were only on the left, including the common iliac, internal iliac and obturator lymph node metastases. Combining preoperative imaging findings and pathological diagnosis, the distribution of multiple lymph node metastases was recorded as predominantly left-sided (Fig. 2C). Although no apparent primary site was identified, lymphatic invasion of HGSC was microscopically detected (Fig. 2D) within the left ovarian parenchyma, and given the distribution of the lymph node metastases, it was suggested that the tumor was left ovary-derived (Fig. 2D). Reevaluation of the pleural fluid cytology image at this point revealed a high nucleus-to-cytoplasmic ratio, which was consistent with an HGSC-like appearance (21). As no primary tumor had been identified, the tumor was diagnosed as a CUP. A CGP test was conducted to diagnose CUP. FoundationOne® CDx (Foundation Medicine, Inc.) is a qualitative next-generation sequencing-based in vitro diagnostic test performed by Foundation Medicine, Inc. (22) that showed 14 somatic variants (Table I), including three likely pathogenic variants [TP53 (p.G266R), CIC (p.E1263Gfs*78) and PBRM1 (p.I223Yfs*36)], and nine gene amplifications of CCND2, CSF3R, FGF23, FGF6, KDM5A, MYC, PIK3C2G, RAD52 and RICTOR (Table II). The tumor was microsatellite-stable with a tumor mutational burden (TMB) of 10.1/Mb (high) and a loss of heterozygosity (LOH) score of 23%. Immune checkpoint inhibitors (ICIs) were recommended based on the tumor being TMB-high (TMB-H) and poly ADP-ribose polymerase (PARP) inhibitors were recommended based on the high LOH score. The tumor distribution, pathological and immunohistochemical examinations, and genomic examinations suggested gynecological organ-derived HGSC (left ovary-derived being suspected). Myriad MyChoice CDx® (Myriad Genetics, Inc.; protocol details not available), a next-generation sequencing-based in vitro diagnostic test performed by Myriad Genetics, Inc., revealed that the tumor was homologous recombination-proficient (HRP) with a homologous recombination-deficiency (HRD) score of 41 and no tumor BRCA1/2 mutation.

Table I.

Somatic variants.

Table I.

Somatic variants.

GeneSitecDNA variationAmino acid substitutionClinical significance
TP5317p13.1c.796G>Ap.G266RLikely pathogenic
CIC19q13.2c.3786_3793delp.E1263Gfs*78Likely pathogenic
GNAS20q13.32 c.*42+13068G>C--
MAF16q23.2 c.543_544insTAC p.Y181_H182insY-
PBRM13p21.1c.666_679delp.I223Yfs*36Likely pathogenic

[i] Summary of gene mutations concluded from next-generation sequencing analysis (FoundationOne® CDx). The tumor mutational burden was 10.1/Mb and the tumor was microsatellite stable. The mean read depth was 1,024 reads. ins, insertion; del, deletion.

Table II.

Copy number alterations.

Table II.

Copy number alterations.

GeneSiteCopy number alterationCopy numberClinical significance
KDM5A12p13.33Amplification10Likely pathogenic

[i] Summary of copy number alterations concluded from next-generation sequencing analysis (FoundationOne® CDx). The mean read depth was 1,024 reads.

The tumor had a high TMB, and ICIs should therefore have been considered; however, the HRD score was 41 (relatively high among HRP tumors) and the LOH score was also high, close to that of the HRD tumor (HRD score ≥42). In addition, HGSC generally has a high response rate to platinum agents and PARP inhibitors are effective only while tumors are platinum-sensitive (2325). Therefore, it was decided to start a combination therapy of paclitaxel and carboplatin (TC therapy; paclitaxel 175 mg/m2 and carboplatin AUC 6 mg/ml/min every 3–4 weeks) and use niraparib (200 mg/body) as maintenance therapy. After eight courses of TC therapy, the CA125 level was markedly reduced from 247 U/ml to 16 U/ml (Fig. 3), and the patient achieved complete remission. Based on the HRD score of 41, the patient was switched to niraparib maintenance therapy according to the treatment protocol for ovarian cancer (25). The patient has been followed up every month since August 2022, when niraparib was started, and will continue to be followed up at the same intervals. The patient has been relapse-free as of July 2023.


In the present case, the diagnosis was delayed by the spontaneous resolution of the cancerous pleural effusion. However, CUP was classified as cancer of ovarian origin based on the marked lymphatic invasion around the left ovary, the distribution of the lymph node metastases, the genomic information and the immunohistochemical data, and the patient was able to receive specific treatment for primary ovarian cancer.

The biological nature of CUP remains largely unknown. The most popular hypothesis is that it is a metastatic tumor arising from an undetectable primary tumor due to regression, dormancy and small size (26,27). Another hypothesis is that it is a single metastatic tumor without a primary tumor (3). The present case is unique in that there was no primary lesion in the uterus and adnexa, accompanied by only lymphatic invasion within the left ovary. These findings suggest that the primary tumor in the left ovary or fallopian tube might either be small or regressed spontaneously.

An important observation in this case was the disappearance of the malignant pleural effusion. To the best of our knowledge, the phenomenon of spontaneous resolution of malignant pleural effusions has not yet been reported, and its precise mechanism remains unresolved. A similar phenomenon, in which a pleural effusion appears with ovarian malignancy and disappears with the disappearance of the ovarian tumor, is known as pseudo-Meigs' syndrome (28,29). In the present case, if the malignant pleural effusion had disappeared with the spontaneous resolution of the primary ovarian tumor, it would be consistent with the pathogenesis of pseudo-Meigs' syndrome.

The reason for the disappearance of the primary tumor was subsequently considered. The patient was being administered systemic exogenous corticosteroids around the time the pleural effusion appeared. It is possible that the systemic administration of steroids suppressed cancer immunity (30). Furthermore, the tumor was TMB-H. HGSC is characterized by copy number alterations with low TMB (3133). TMB-H tumors are characterized by high levels of neoantigens and immunogenicity (34). One hypothesis is that the patient developed highly immunogenic ovarian cancer, but that cancer immunity was suppressed during steroid administration, resulting in pseudo-Meigs' syndrome associated with ovarian cancer. Subsequent reactivation of immunity by steroid withdrawal may have triggered shrinkage of the primary tumor and disappearance of the pleural effusion.

In the present case, genomic data suggested that PARP inhibitors could be expected to be effective as maintenance therapy after TC therapy. In addition, the patient had a TMB-H tumor and was expected to benefit from ICIs. Although the patient was treated with TC therapy followed by maintenance therapy with a PARP inhibitor based on the treatment regimen for primary ovarian cancer, the efficacy of immunotherapy in CUP has been demonstrated in a phase II trial (35) and is expected to become more widespread in the future. Approximately one-third of patients with CUP have a tumor proportion score >1% for programmed cell death 1-ligand 1, and antitumor immunity-related gene expression in CUP have been reported to be comparable to those in ICI-responsive malignancies (36,37). The pleural effusion appeared at the time of steroid administration and the tumor was a TMB-H tumor, which is rare for ovarian HGSC (31,32). This may suggest that the pathophysiology of CUP in the present case report is highly immunogenic.

The present study had some limitations. First, the hypothesis of pseudo-Meigs' syndrome associated with ovarian cancer was proposed as a pathogenesis of CUP; however, it is not possible to prove this hypothesis since there was no evidence of a tumor in the left ovary. Second, based on the high LOH score, a PARP inhibitor was used after TC therapy; however, it was not possible to evaluate the response to the PARP inhibitor, as the TC therapy resulted in complete remission. Long-term observations are needed in the future to investigate the effects of PARP inhibitors and ICIs.

In the present case, lymphatic invasion, the distribution of the lymph node metastases, genomic analysis and immunohistological analysis suggested CUP of left ovarian origin, and specific therapy for ovarian cancer was provided. This unique course, which was characterized by the appearance and disappearance of the CUP, may have been associated with the immune response.


Not applicable.


Funding: No funding was received.

Availability of data and materials

The sequencing datasets generated and/or analyzed during the current study are not publicly available as the Myriad MyChoice CDx® and FoundationOne® CDx reports are all the raw data that Foundation Medicine, Inc., and Myriad Genetics, Inc. can provide. All content from the reports has been provided in the manuscript. It has been confirmed with Chugai Pharmaceutical Co., and Myriad Genetics, Inc., that no other data will be provided. The other datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Authors' contributions

HH and AT conceived and designed the study. HH, AT, HR, AM, AN, TA, SE, YM, KS, MUM and YO obtained data and treated this patient. HH analyzed the data and drafted the manuscript. HR analyzed the data using pathological methods. HH and HR confirm the authenticity of the pathological data. HH and AT confirm the authenticity of all other raw data. AT, HR, AM, TA, AN, SE, YM, KS, MUM and YO revised the manuscript before submission. All authors read and approved the final version of the manuscript.

Ethics approval and consent to participate

This case received standard clinical treatment as a cancer of unknown primary equivalent to ovarian cancer. For this report, in accordance with the Act on the Protection of Personal Information in Japan (38), this study was approved by the Institutional Ethics Committee of The University of Tokyo (approval no. G0683; Tokyo, Japan).

Patient consent for publication

The patient provided written informed consent for publication of any associated data and accompanying images.

Competing interests

The authors declare that they have no competing interests.





cancer of unknown primary


cancer genomic profiling


positron emission tomography-computed tomography


high-grade serous carcinoma


tumor mutational burden




immune checkpoint inhibitor


homologous recombination-proficient


homologous recombination-deficiency

TC therapy

paclitaxel-carboplatin combination therapy


standardized uptake value


cancer antigen 125


poly ADP-ribose polymerase



Varadhachary GR and Raber MN: Cancer of unknown primary site. N Engl J Med. 371:757–765. 2014. View Article : Google Scholar : PubMed/NCBI


Qaseem A, Usman N, Jayaraj JS, Janapala RN and Kashif T: Cancer of unknown primary: A review on clinical guidelines in the development and targeted management of patients with the unknown primary site. Cureus. 11:e55522019.PubMed/NCBI


Kato S, Alsafar A, Walavalkar V, Hainsworth J and Kurzrock R: Cancer of unknown primary in the molecular Era. Trends Cancer. 7:465–477. 2021. View Article : Google Scholar : PubMed/NCBI


Pavlidis N and Pentheroudakis G: Cancer of unknown primary site. Lancet. 379:1428–1435. 2012. View Article : Google Scholar : PubMed/NCBI


Pavlidis N, Khaled H and Gaafar R: A mini review on cancer of unknown primary site: A clinical puzzle for the oncologists. J Adv Res. 6:375–382. 2015. View Article : Google Scholar : PubMed/NCBI


Pavlidis N, Briasoulis E, Hainsworth J and Greco FA: Diagnostic and therapeutic management of cancer of an unknown primary. Eur J Cancer. 39:1990–2005. 2003. View Article : Google Scholar : PubMed/NCBI


Hannouf MB, Winquist E, Mahmud SM, Brackstone M, Sarma S, Rodrigues G, Rogan PK, Hoch JS and Zaric GS: The potential clinical and economic value of primary tumour identification in metastatic cancer of unknown primary tumour: A population-based retrospective matched cohort study. Pharmacoecon Open. 2:255–270. 2018. View Article : Google Scholar : PubMed/NCBI


Yang H, He F, Xu W and Cao Z: Clinical features of cancer with unknown primary site (clinical features, treatment, prognosis of cancer with unknown primary site). BMC Cancer. 22:13722022. View Article : Google Scholar : PubMed/NCBI


Hainsworth JD, Rubin MS, Spigel DR, Boccia RV, Raby S, Quinn R and Greco FA: Molecular gene expression profiling to predict the tissue of origin and direct site-specific therapy in patients with carcinoma of unknown primary site: A prospective trial of the Sarah Cannon research institute. J Clin Oncol. 31:217–223. 2013. View Article : Google Scholar : PubMed/NCBI


Greco FA, Lennington WJ, Spigel DR and Hainsworth JD: Molecular profiling diagnosis in unknown primary cancer: Accuracy and ability to complement standard pathology. J Natl Cancer Inst. 105:782–790. 2013. View Article : Google Scholar : PubMed/NCBI


Varadhachary GR, Talantov D, Raber MN, Meng C, Hess KR, Jatkoe T, Lenzi R, Spigel DR, Wang Y, Greco FA, et al: Molecular profiling of carcinoma of unknown primary and correlation with clinical evaluation. J Clin Oncol. 26:4442–4448. 2008. View Article : Google Scholar : PubMed/NCBI


Hayashi H, Kurata T, Takiguchi Y, Arai M, Takeda K, Akiyoshi K, Matsumoto K, Onoe T, Mukai H, Matsubara N, et al: Randomized phase II trial comparing site-specific treatment based on gene expression profiling with carboplatin and paclitaxel for patients with cancer of unknown primary site. J Clin Oncol. 37:570–579. 2019. View Article : Google Scholar : PubMed/NCBI


Moran S, Martínez-Cardús A, Sayols S, Musulén E, Balañá C, Estival-Gonzalez A, Moutinho C, Heyn H, Diaz-Lagares A, de Moura MC, et al: Epigenetic profiling to classify cancer of unknown primary: A multicentre, retrospective analysis. Lancet Oncol. 17:1386–1395. 2016. View Article : Google Scholar : PubMed/NCBI


Laprovitera N, Salamon I, Gelsomino F, Porcellini E, Riefolo M, Garonzi M, Tononi P, Valente S, Sabbioni S, Fontana F, et al: Genetic characterization of cancer of unknown primary using liquid biopsy approaches. Front Cell Dev Biol. 9:6661562021. View Article : Google Scholar : PubMed/NCBI


Pauli C, Bochtler T, Mileshkin L, Baciarello G, Losa F, Ross JS, Pentheroudakis G, Zarkavelis G, Yalcin S, Özgüroğlu M, et al: A challenging task: Identifying patients with cancer of unknown primary (CUP) According to ESMO Guidelines: The CUPISCO trial experience. Oncologist. 26:e769–e779. 2021. View Article : Google Scholar : PubMed/NCBI


Pisacane A, Cascardi E, Berrino E, Polidori A, Sarotto I, Casorzo L, Panero M, Boccaccio C, Verginelli F, Benvenuti S, et al: Real-world histopathological approach to malignancy of undefined primary origin (MUO) to diagnose cancers of unknown primary (CUPs). Virchows Arch. 482:463–475. 2023. View Article : Google Scholar : PubMed/NCBI


Uchikura E, Fukuda T, Imai K, Yamauchi M, Kasai M, Ichimura T, Yasui T, Kuwae Y and Sumi T: Carcinomatous meningitis from ovarian serous carcinoma: A case report. Oncol Lett. 25:662022.PubMed/NCBI


Papanicolaou GN: Atlas of Exfoliative Cytology. Cambridge, Mass: Harvard University Press; 1954


Hinata M, Kunita A, Abe H, Morishita Y, Sakuma K, Yamashita H, Seto Y, Ushiku T and Fukayama M: Exosomes of epstein-barr virus-associated gastric carcinoma suppress dendritic cell maturation. Microorganisms. 8:17762020. View Article : Google Scholar : PubMed/NCBI


WHO Classification of Tumours Editorial Board, . Female Genital Tumors, WHO Classification of Tumors. Vol 4:(5th edition). 2020.


Pereira TC, Saad RS, Liu Y and Silverman JF: The diagnosis of malignancy in effusion cytology: A pattern recognition approach. Adv Anat Pathol. 13:174–184. 2006. View Article : Google Scholar : PubMed/NCBI


Milbury CA, Creeden J, Yip WK, Smith DL, Pattani V, Maxwell K, Sawchyn B, Gjoerup O, Meng W, Skoletsky J, et al: Clinical and analytical validation of FoundationOne® CDx, a comprehensive genomic profiling assay for solid tumors. PLoS One. 17:e02641382022. View Article : Google Scholar : PubMed/NCBI


Moore K, Colombo N, Scambia G, Kim BG, Oaknin A, Friedlander M, Lisyanskaya A, Floquet A, Leary A, Sonke GS, et al: Maintenance olaparib in patients with newly diagnosed advanced ovarian cancer. N Engl J Med. 379:2495–2505. 2018. View Article : Google Scholar : PubMed/NCBI


González-Martín A, Pothuri B, Vergote I, DePont Christensen R, Graybill W, Mirza MR, McCormick C, Lorusso D, Hoskins P, Freyer G, et al: Niraparib in patients with newly diagnosed advanced ovarian cancer. N Engl J Med. 381:2391–2402. 2019. View Article : Google Scholar : PubMed/NCBI


Coleman RL, Fleming GF, Brady MF, Swisher EM, Steffensen KD, Friedlander M, Okamoto A, Moore KN, Efrat Ben-Baruch N, Werner TL, et al: Veliparib with first-line chemotherapy and as maintenance therapy in ovarian cancer. N Engl J Med. 381:2403–2415. 2019. View Article : Google Scholar : PubMed/NCBI


Olivier T, Fernandez E, Labidi-Galy I, Dietrich PY, Rodriguez-Bravo V, Baciarello G, Fizazi K and Patrikidou A: Redefining cancer of unknown primary: Is precision medicine really shifting the paradigm? Cancer Treat Rev. 97:1022042021. View Article : Google Scholar : PubMed/NCBI


Conway AM, Mitchell C, Kilgour E, Brady G, Dive C and Cook N: Molecular characterisation and liquid biomarkers in Carcinoma of Unknown Primary (CUP): taking the ‘U’ out of ‘CUP’. Br J Cancer. 120:141–153. 2019. View Article : Google Scholar : PubMed/NCBI


Kazanov L, Ander DS, Enriquez E and Jaggi FM: Pseudo-Meigs' Syndrome. Am J Emerg Med. 16:404–405. 1998. View Article : Google Scholar : PubMed/NCBI


Gücer F, Oz-Puyan F, Mülayim N and Yüce MA: Ovarian dysgerminoma associated with Pseudo-Meigs' syndrome and functioning ovarian stroma: A case report. Gynecol Oncol. 97:681–684. 2005. View Article : Google Scholar : PubMed/NCBI


Coutinho AE and Chapman KE: The anti-inflammatory and immunosuppressive effects of glucocorticoids, recent developments and mechanistic insights. Mol Cell Endocrinol. 335:2–13. 2011. View Article : Google Scholar : PubMed/NCBI


Cristescu R, Mogg R, Ayers M, Albright A, Murphy E, Yearley J, Sher X, Lin XQ, Lu H, Nebozhyn M, et al: Pan-tumor genomic biomarkers for PD-1 checkpoint blockade-based immunotherapy. Science. 362:eaar35932018. View Article : Google Scholar : PubMed/NCBI


Park J, Lee JY and Kim S: How to use immune checkpoint inhibitor in ovarian cancer? J Gynecol Oncol. 30:e1052019. View Article : Google Scholar : PubMed/NCBI


Leary A, Tan D and Ledermann J: Immune checkpoint inhibitors in ovarian cancer: Where do we stand? Ther Adv Med Oncol. 13:175883592110398992021. View Article : Google Scholar : PubMed/NCBI


Ward JP, Gubin MM and Schreiber RD: The role of neoantigens in naturally occurring and therapeutically induced immune responses to cancer. Adv Immunol. 130:25–74. 2016. View Article : Google Scholar : PubMed/NCBI


Raghav KP, Stephen B, Karp DD, Piha-Paul SA, Hong DS, Jain D, Chudy Onwugaje DO, Abnofal A, Willett AF, Overman M, et al: Efficacy of pembrolizumab in patients with advanced cancer of unknown primary (CUP): A phase 2 non-randomized clinical trial. J Immunother Cancer. 10:e0048222022. View Article : Google Scholar : PubMed/NCBI


Tanizaki J, Yonemori K, Akiyoshi K, Minami H, Ueda H, Takiguchi Y, Miura Y, Segawa Y, Takahashi S, Iwamoto Y, et al: Open-label phase II study of the efficacy of nivolumab for cancer of unknown primary. Ann Oncol. 33:216–226. 2022. View Article : Google Scholar : PubMed/NCBI


Haratani K, Hayashi H, Takahama T, Nakamura Y, Tomida S, Yoshida T, Chiba Y, Sawada T, Sakai K, Fujita Y, et al: Clinical and immune profiling for cancer of unknown primary site. J Immunother Cancer. 7:2512019. View Article : Google Scholar : PubMed/NCBI


Japanese government, . Act on the Protection of Personal Information: Last Version: Act No. 37 of 2021. Translated Date: November 5, 2021. 24–2023

Related Articles

Journal Cover

Volume 26 Issue 6

Print ISSN: 1792-1074
Online ISSN:1792-1082

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
Spandidos Publications style
Honjoh H, Taguchi A, Rokutan H, Mori A, Ando T, Nishijima A, Eguchi S, Miyamoto Y, Sone K, Uchino‑Mori M, Uchino‑Mori M, et al: Cancer of unknown primary histologically, genetically and spatially diagnosed as left ovary‑derived cancer: A case report. Oncol Lett 26: 522, 2023
Honjoh, H., Taguchi, A., Rokutan, H., Mori, A., Ando, T., Nishijima, A. ... Osuga, Y. (2023). Cancer of unknown primary histologically, genetically and spatially diagnosed as left ovary‑derived cancer: A case report. Oncology Letters, 26, 522.
Honjoh, H., Taguchi, A., Rokutan, H., Mori, A., Ando, T., Nishijima, A., Eguchi, S., Miyamoto, Y., Sone, K., Uchino‑Mori, M., Osuga, Y."Cancer of unknown primary histologically, genetically and spatially diagnosed as left ovary‑derived cancer: A case report". Oncology Letters 26.6 (2023): 522.
Honjoh, H., Taguchi, A., Rokutan, H., Mori, A., Ando, T., Nishijima, A., Eguchi, S., Miyamoto, Y., Sone, K., Uchino‑Mori, M., Osuga, Y."Cancer of unknown primary histologically, genetically and spatially diagnosed as left ovary‑derived cancer: A case report". Oncology Letters 26, no. 6 (2023): 522.