A 56-year-old man presented to our hospital with dyspnea on exertion for two months. Bilateral pleural effusions were found, and a close examination revealed a chylothorax, including adenocarcinoma. The primary tumor could not be identified by systemic examination. Therefore, the patient was diagnosed with cancer of unknown primary origin (CUP) presenting with chylothorax. Chemotherapy was administered for CUP, and thoracentesis, pleurodesis, ascites puncture, and nutritional therapy were performed for chylothorax and chylous ascites. Although drainage frequency and tumor marker levels (CA19-9, DUPAN-2, and Span-1) temporarily decreased, disease control deteriorated, and the patient died 12 months after the initial diagnosis.

Cancer of unknown primary (CUP) and leptomeningeal metastasis are difficult conditions with limited treatment options. We report a case of CUP leptomeningeal metastasis that was refractory to empirical chemotherapy but achieved a favorable response to intrathecal trastuzumab after the identification of human epidermal growth factor receptor-2 (HER2) amplification. A 59-year-old woman was diagnosed with CUP with metastasis of a poorly differentiated carcinoma to the left axillary, anterior mediastinal, peritoneal, and bilateral supraclavicular lymph nodes. Leptomeningeal metastasis was confirmed shortly after she started empiric chemotherapy; empiric therapy with intrathecal methotrexate failed to relieve her symptoms. Meanwhile, the lymph node specimen tested positive for HER2 amplification. She underwent intrathecal trastuzumab, then her neurological symptoms resolved the following day. We suggest that intrathecal trastuzumab is an effective treatment for HER2-positive CUP leptomeningeal metastasis.

BACKGROUND: Even in cancer of unknown primary (CUP), which is rare clinical condition, solitary anterosuperior lymph node (LN) along the common hepatic artery (No.8a LN) enlargement diagnosed as metastatic adenocarcinoma has never been reported.
METHODS: A 68-year-old Japanese male, with a history of early gastric cancer that had been completely treated by endoscopic submucosal dissection 26 years ago, was detected a single enlarged nodule along the common hepatic artery, No.8a LN, incidentally by computed tomography performed for monitoring of interstitial pneumonia. Endoscopic ultra-sound-guided fine needle aspiration revealed that this nodule was adenocarcinoma suggestive of metastasis, but other imaging studies, including upper and lower gastrointestinal endoscopy, positron emission tomography, and ultrasonography did not detect any primary cancer. We have finally diagnosed as the LN metastasis of CUP and performed laparoscopic lymphadenectomy for this tumor. The tumor was approximately 5 cm in size, was in close proximity to the pancreas, and involved part of the right gastric artery and vein. LNs in the No.5 and No.8a areas, including this tumor, were dissected laparoscopically, and radical resection was achieved. The patient had no postoperative complication and was discharged on postoperative day 10. Immunohistopathological findings revealed that the tumor was poorly differentiated adenocarcinoma, and different from the histology of gastric cancer resected 26 years ago, although the tumor was suggestive of gastrointestinal origin. Imaging studies performed 2 and 6 months after discharge also did not reveal a primary site.
CONCLUSIONS: We reported a case of solitary No.8a LN adenocarcinoma of CUP. For diagnostic and therapeutic purposes, radical resection is recommended for single enlarged intra-abdominal LN of CUP.

UNASSIGNED: Cancer of unknown primary (CUP) is a tumour metastasis with no detectable primary origin. A secondary neoplasm (SN) is defined as a tumour secondary to a prior tumour treatment and has no histological relation to that primary tumour.
UNASSIGNED: The authors report a case of a 72-year-old female patient who presented with back pain and had a history of non-Hodgkin lymphoma (NHL) treated with RCHOP 12 years ago. MRI showed a compression fracture in T5 and T7 vertebrae, while the PET/computed tomography (CT) only showed hypermetabolic lytic bone lesions in these vertebrae. Pathological examination of a biopsy of these lesions suggested metastatic breast cancer, but the mammography was normal. The above clinical description indicates that our case is a SN to RCHOP treatment manifested as a cancer of unknown origin.
UNASSIGNED: CUP is diagnosed when all screening procedures fail to find the original tumour. On the other hand, the literature showed that RCHOP treatment of non-Hodgkin lymphoma has a 0.68% chance of causing a SN. After an extensive literature search, we found that our case, which has the combination of both CUP and SN, is the first documented case.
UNASSIGNED: This case suggests that cancer patients who received chemical or radiological treatment should be screened more carefully on the long term as it is possible to developed secondary neoplasms without a primary tumour in areas difficult to diagnose with traditional screening tools.

Cancer of unknown primary (CUP) is a heterogeneous disease concept involving various malignant tumors. Understanding its pathophysiology is often difficult, together with its treatment. Here, we present a case of CUP with abdominal lymph node enlargement and elevated carbohydrate antigen 125 levels. It initially resembled a favorable prognosis type similar to ovarian cancer, but metastases were observed in cervical lymph nodes, indicating a somewhat atypical CUP compared to the typical ovarian cancer-like CUP. We identified a germline Breast Cancer 1 (BRCA1) p.L63* variant through a family history inquiry and BRCA analysis, indicating hereditary breast and ovarian cancer syndrome. The patient achieved near-complete remission with platinum-based therapy followed by poly (ADP-ribose) polymerase (PARP) inhibitor. The variant has shown sensitivity in both clinical and pathogenic reports in the ClinVar database of the National Institutes of Health. No clinical studies reported on the efficacy of PARP inhibitors specific to this variant, but our case demonstrated the sensitivity of platinum-based therapy followed by PARP inhibitor. Reports of CUP in hereditary breast and ovarian cancer syndrome are very rare, with only a single report in the literature.

Cancer of unknown primary (CUP) represents a significant diagnostic and therapeutic challenge, being the third to fourth leading cause of cancer death, despite advances in diagnostic tools. This article presents a successful approach using a novel genomic analysis in the evaluation and treatment of a CUP patient, leveraging whole-exome sequencing (WES) and RNA sequencing (RNA-seq). The patient, with a history of multiple primary tumors including urothelial cancer, exhibited a history of rapid progression on empirical chemotherapy. The application of our approach identified a molecular target, characterized the tumor expression profile and the tumor microenvironment, and analyzed the origin of the tumor, leading to a tailored treatment. This resulted in a substantial radiological response across all metastatic sites and the predicted primary site of the tumor. We argue that a comprehensive genomic and molecular profiling approach, like the BostonGene© Tumor Portrait, can provide a more definitive, personalized treatment strategy, overcoming the limitations of current predictive assays. This approach offers a potential solution to an unmet clinical need for a standardized approach in identifying the tumor origin for the effective management of CUP.

OBJECTIVE: Metastatic squamous cell carcinoma (SCC) of inguinal lymph node region with unknown origin is a rare condition. A patient was diagnosed to have vulvar SCC 7 years after the initial diagnosis of inguinal nodal metastatic SCC of unknown primary.
METHODS: A 59-year-old woman with metastatic SCC of unknown origin in the right inguinal lymph node underwent tumor resection and no evidence of residual disease or possible tumor origin was detected after the surgery and a comprehensive work-up. Seven years later, she was diagnosed to have invasive right vulvar SCC with right pelvic lymph node metastasis. We performed a series of tests to evaluate the relationship between these two events.
CONCLUSIONS: According to our investigation, the possible relationship between the two events could not be ruled out. This case emphasizes the possibility of late recurrence and the importance of long-term follow up for patients with isolated nodal CUP.

BACKGROUND: Although 25-30 % of renal cell carcinomas (RCC) might be diagnosed in metastatic stage, occurrence of metastatic renal cell carcinoma (mRCC) as a cancer of unknown primary site (CUP-mRCC) is extremely rare. Here, we present a case of vertebral mass causing radicular pain that has been diagnosed to be mRCC through core needle biopsy while no renal mass has been found during serial imaging.
METHODS: A 60-year-old woman presented with severe lumbar pain radiating to left leg. Lumbar X-ray suggested a mass in second lumbar vertebra which was confirmed by MRI. Biopsy showed that the mass was clear cell RCC. Abdominopelvic CT scan and other metastatic work-up found no primary source for the cancer -in kidneys- nor any other metastasis. Tumor resection was performed followed by sunitinib administration. 3 months after the surgery, she is symptom free with no signs of disease progression nor kidney tumor.
CONCLUSIONS: 26 cases of CUP-mRCC has been reported in literature. Lymph nodes are the most commonly involved organ in CUP-mRCC. Exclusive bone involvement -similar to our case- have been reported in only 3 cases. No specific treatment guideline exists but surgery, systemic therapy, combination therapy, and radiotherapy have been used, with the first two items being the most commonly used ones.
CONCLUSIONS: Tumor resection plus sunitinib seems to be a reasonable option in solitary CUP-mRCC involving vertebral column. Our patient is symptom free and there are no signs of disease progression nor kidney cancer in follow-up imaging after 3 months of surgery.

Cancers of unknown primary (CUP) account for 2%-5% of all diagnosed cancers and are always characterized with fast-paced aggression, early metastasis, and unpredictable spread patterns Mediastinum metastasis with unknown primary origin is extremely rare and with a poor prognosis and short survival. There is no literature to refer to for its treatment. Here, we reported a case of squamous cell CUP in the mediastinum. A 50-year-old male patient was admitted after multi-line treatment of low differentiated squamous cell carcinoma in the mediastinum diagnosed 8 months before. In August 2019, the patient went to a local hospital for cough and dyspnea for 2 weeks. Then, he was diagnosed with squamous cell carcinoma of unknown primary origin with multiple lymph nodes metastasis. The patient was featured with programmed cell death-ligand 1 (PD-L1) expression strongly positive in 90% of tumor cells and the combined positive score of 90 and a tumor mutation burden of 1.79 MUts/Mb and microsatellite stable phenotype. The patient was treated with anti-programmed cell death-1 (PD-1) antibodies in combination with chemotherapy and responded to the treatment. The patient showed stable disease to multi-line immunotherapy for more than 7 months and finally got a clinical benefit of 2-year survival benefit. In conclusion, immunotherapy targeting PD-1/PD-L1 in combination with chemotherapy may play a crucial role in the later-line treatment and palliative care of CUP.

Cancer of unknown primary (CUP) is a heterogeneous group of metastatic tumors in the absence of a clinically identifiable site. We describe the case of a 66-year-old female with an extensive history of non-specific imaging concerning for malignancy who did not undergo further workup and in whom a diagnosis of CUP was made. The patient initially presented to her specialist with concern of right leg pain. Imaging at that time was concerning for a progressive malignant process. Given this, the patient was referred urgently for surgery. Final surgical pathology and breast prognostic panel were consistent with metastatic breast carcinoma at that time. Follow-up imaging performed 1-week postoperatively did not show suspicious findings in either breast, further supporting a diagnosis of CUP. To this end, we highlight the importance of follow-up imaging but recognize the challenges facing healthcare professionals in navigating the ethical principles of nonmalificience and beneficence in diagnostic workup.