[Analysis of cases of cervical cystic lymph node metastasis with an unknown primary misdiagnosed as branchial cleft carcinoma].

Objectives: To analyze the location, discovery time and possible causes of cases of cervical cystic lymph node metastasis with an unknown primary misdiagnosed as branchial cleft carcinoma. Methods: A retrospective analysis was performed on clinical and pathological data of 15 patients misdiagnosed as branchiogenic carcinoma at Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College between January 2000 and December 2020. Results: Among the 15 patients, 6 were nasopharyngeal squamous cell carcinoma, 4 tonsil squamous cell carcinoma, 2 tongue root squamous cell carcinoma, 2 hypopharyngeal squamous cell carcinoma and 1 thyroid papillary carcinoma. The median time from the diagnosis of branchial cleft carcinoma to the discovery of primary lesions was 3.58 months (0-76 months). The causes of misdiagnosis might be the lack of experience in the diagnosis and treatment of branchial cleft carcinoma, and not enough attention to comprehensive examination and close follow-up. Conclusions: Different from oropharyngeal cancer reported internationally, the proportion of misdiagnosed cases with nasopharyngeal carcinoma as the primary site in the current article is higher. As a country with a high incidence of nasopharyngeal carcinoma, the examination of nasopharynx should not be taken lightly. Most hidden cases can be found in the comprehensive examination in a short time, while a few cases need long-term follow-up. Finding the primary sites should not rely too much on imaging examination, and we cannot ignore the importance of clinical physical examination.

Programmed death-ligand 1 expression in carcinoma of unknown primary.

We examined the expression of programmed death-ligand 1 (PD-L1) in carcinoma of unknown primary (CUP) and its potential implications. Tissue microarrays were constructed for 72 CUP cases (histologic subtypes: 22 adenocarcinoma, 15 poorly differentiated carcinoma, 19 squamous cell carcinoma, and 14 undifferentiated carcinoma; clinical subtype: favorable type 17 [23.6%], unfavorable type 55 [76.4%]), with immunohistochemical staining performed for PD-L1 (22C3, SP142, SP263, and 28 - 8), CK7, and CK20 to determine the association between staining results and clinicopathological parameters. In CUP, the PD-L1 positivity rate was 5.6-48.6% (tumor cells [TC] or tumor proportion score [TPS]: 5.6-36.1%, immune cell score [IC]: 8.3-48.6%, combined positive score [CPS]: 16.7%) using different cutoff values for 22C3 (TPS ≥ 1%, CPS ≥ 10), SP142 (TC ≥ 50%, IC ≥ 10%), SP263, and 28 - 8 (TC and IC ≥ 1%). PD-L1 SP142 TC and PD-L1 SP263 IC showed the lowest (5.6%) and highest (48.6%) positivity rates, respectively. The PD-L1 positivity rate did not significantly differ based on the histologic subtype, clinical subtype, or CK7/CK20 across clones. Considering TC κ ≥ 1%, TC κ ≥ 50%, IC κ ≥ 1%, and IC κ ≥ 10%, the PD-L1 positivity rate was TC = 4.2-36.1% and IC = 9.7-48.6%; the overall agreement between antibodies ranged from 69.4 to 93.1%, showing fair or better agreement (κ ≥ 0.21). In CUP, PD-L1 positivity varied depending on antibodies and scoring systems, with no difference observed according to histologic or clinical subtypes.

[Cervical CUP Syndrome: Diagnosis and Therapy]. / Zervikales CUP-Syndrom: Diagnostik und Therapie.

In CUP syndrome (CUP = cancer of unknown primary) there are 1 or more metastases of a primary tumor that cannot be localized despite extensive diagnostics. CUP syndrome accounts for 5% of all human malignancies, making it one of the 10 most common forms of cancer. In addition to inflammatory lymph node enlargement and benign changes such as cervical cysts, lymph node metastases are among the most common cervical masses. Cervical CUP syndrome is a histologically confirmed cervical lymph node metastasis with an unknown primary tumor. In addition to anamnesis, clinical examination and histological confirmation, diagnostics include radiological imaging using PET-CT and panendoscopy with histological primary tumor search. Treatment options include surgical therapy with neck dissection and chemoradiotherapy.

Clinicopathologic features and genomic profiling of female axillary lymph node metastases from adenocarcinoma or poorly differentiated carcinoma of unknown primary.

PURPOSE: Axillary lymph node metastases from adenocarcinoma or poorly differentiated carcinoma of unknown primary (CUPAx) is a rare disease in women. This retrospective study intended to examine the clinicopathological features of CUPAx and compared CUPAx genetically with axillary lymph node metastases from breast cancer (BCAx), investigating differences in their biological behavior. METHODS: We conducted the clinical and prognostic analysis of 58 CUPAx patients in West China Hospital spanning from 2009 to 2021. Gemonic profiling of 12 CUPAx patients and 16 BCAx patients was conducted by the FoundationOne CDx (F1CDx) platform. Moreover, we also compared the gene mutation spectrum and relevant pathways between the two groups and both TCGA and COSMIC databases. RESULTS: The majority of the 58 CUPAx patients were HR-/HER2- subtype. Most patients received mastectomy combined radiotherapy (50 Gy/25f). CUPAx patients who received mastectomy instead of breast-conserving surgery had a more favorable overall prognosis. Radiotherapy in chest wall/breast and supraclavicular/infraclavicular fossa was the independent prognostic factor (HR = 0.05, 95%CI = 0.00-0.93, P = 0.04). In 28 sequencing samples (CUPAx, n = 12, BCAx, n = 16) and 401 TCGA-BRCA patients, IRS2 only mutated in CUPAx (33.33%) but amplified in BCAx (11.11%) and TCGA-BRCA (1.5%). Pathway analysis revealed that BCAx had more NOTCH pathway mutations than CUPAx. Enrichment analysis showed that CUPAx enriched more in mammary development and PML bodies than BCAx, but less in the positive regulation of kinase activity. CONCLUSIONS: More active treatment methods, like chemotherapy, mastectomy and postoperative radiotherapy, could improve the prognosis of CUPAx. The differential mutation genes of CUPAx and BCAx might be associated with their respective biological behaviors like invasiveness and prognosis.

[Swelling on the neck]. / Schwellung am Hals.

INTRODUCTION: A 30-year-old female patient presented with a swelling of a cervical left lymph node measuring 1x3 cm, which had been presenting for three weeks. Lymph node excision revealed a metastasis of a malignant melanoma, but the primary tumor was not found. The guidelines recommend neck dissection and adjuvant systemic or immunotherapy. The patient opted for immunotherapy with pembrolizumab and was tumor-free one year later.

Prediction of tumor origin in cancers of unknown primary origin with cytology-based deep learning.

Cancer of unknown primary (CUP) site poses diagnostic challenges due to its elusive nature. Many cases of CUP manifest as pleural and peritoneal serous effusions. Leveraging cytological images from 57,220 cases at four tertiary hospitals, we developed a deep-learning method for tumor origin differentiation using cytological histology (TORCH) that can identify malignancy and predict tumor origin in both hydrothorax and ascites. We examined its performance on three internal (n = 12,799) and two external (n = 14,538) testing sets. In both internal and external testing sets, TORCH achieved area under the receiver operating curve values ranging from 0.953 to 0.991 for cancer diagnosis and 0.953 to 0.979 for tumor origin localization. TORCH accurately predicted primary tumor origins, with a top-1 accuracy of 82.6% and top-3 accuracy of 98.9%. Compared with results derived from pathologists, TORCH showed better prediction efficacy (1.677 versus 1.265, P < 0.001), enhancing junior pathologists' diagnostic scores significantly (1.326 versus 1.101, P < 0.001). Patients with CUP whose initial treatment protocol was concordant with TORCH-predicted origins had better overall survival than those who were administrated discordant treatment (27 versus 17 months, P = 0.006). Our study underscores the potential of TORCH as a valuable ancillary tool in clinical practice, although further validation in randomized trials is warranted.

Transoral Robotic Surgery and Radiation Volume Deintensification in Unknown Primary Squamous Cell Carcinoma of the Neck: The Phase 2 FIND Nonrandomized Controlled Trial.

Importance: Patients with unknown primary squamous cell carcinoma (CUP) with cervical metastases typically receive comprehensive radiotherapy (RT) of the pharynx and bilateral neck. Typically, these patients receive comprehensive RT of the pharynx and bilateral neck that may produce treatment-related toxic effects. Objective: To determine whether localization of occult oropharyngeal cancers with transoral robotic surgery (TORS) combined with reduced pharyngeal and neck RT volumes provides acceptable disease control. Design, Setting, and Participants: This phase 2, single-group nonrandomized controlled trial at a single institution accrued 32 prospective participants with p16-positive CUP without a primary squamous cell carcinoma on examination and imaging from 2017 to 2019, and 24-month follow-up. The data analysis was conducted from January 2021 to June 2022. Intervention: Diagnostic- (n = 13) or therapeutic-intent (n = 9) TORS, with pharyngeal-sparing radiotherapy (PSRT) prescribed for negative margins or pT0, and unilateral neck RT (UNRT) prescribed for unilateral lymphadenopathy with lateralized primary tumor or pT0. Main Outcomes and Measures: Out-of-radiation treatment volume failure (<15% was hypothesized to be acceptable) and reports of local and regional recurrence, overall survival, toxic effects, swallowing outcomes (per the MD Anderson Dysphagia Inventory), and videofluoroscopic swallow (per Dynamic Imaging Grade of Swallowing Toxic Effects [DIGEST]) ratings. Results: The study sample comprised 22 patients (mean [SD] age, 59.1 [5.7] years; 3 [14%] females and 19 [86%] male) with CUP. Of these, 19 patients (86%) had tumor stage cN1; 2 (9%), cN2; and 1 (5%), cN3. Five patients (23%), 14 patients (64%), and 3 patients (13%) had 0, 1, or 2 primary tumors, respectively. Twenty patients received RT; of these, 9 patients (45%) underwent PSRT and 10 patients (50%), UNRT. In the diagnostic-intent group, 8 patients (62%) and 5 patients (38%) underwent RT and RT-concurrent chemotherapy, respectively. In the therapeutic-intent group, 6 patients (67%) and 1 patient (11%) received adjuvant RT-concurrent chemotherapy, respectively; 2 patients declined RT. Two-year out-of-radiation treatment volume failure, locoregional control, distant metastasis control, and overall survival were 0%, 100%, 95%, and 100%, respectively. Grade 3 or 4 surgical, acute, and late toxic effects occurred in 2 (9%), 5 (23%), and 1 (5%) patients, respectively. PSRT was associated with lower RT dose to superior constrictors (37 vs 53 Gy; mean difference, 16 Gy; 95% CI, 6.4, 24.9), smaller decline in swallowing scores during treatment (19.3 vs 39.7; mean difference, -20.4; 95% CI, -34.1 to -6.1), and fewer patients with worsening DIGEST grade on findings of videofluoroscopic swallow studies at 2 years (0% vs 60%; difference, 60%; 95% CI, 30% to 90%). Conclusions and Relevance: These findings indicate that TORS for p16-positive CUP allows RT volume deintensification with excellent outcomes and support future investigation in randomized clinical trials. Trial Registration: ClinicalTrials.gov Identifier: NCT03281499.

Retrospective analysis of clinical characteristics and outcomes of patients with carcinoma of unknown primary from three tertiary centers in Australia.

BACKGROUND: Carcinoma of unknown primary (CUP) remains an important tumor entity and a disproportionate cause of cancer mortality. Little is known about the contemporary clinical characteristics, treatment patterns, and outcomes of CUP patients based on updated international classification guidelines. We evaluated a contemporary CUP cohort to provide insight into current clinical practice and the impact of tissue of origin assignment, site-specific and empirical therapy in a real-world setting. METHODS: We conducted a retrospective cohort study of CUP patients, as defined by the updated European Society of Medical Oncology (ESMO) 2023 guidelines, across three tertiary referral centers in Australia between 2015 and 2022. We analyzed clinical characteristics, treatment patterns, and survival outcomes using the Kaplan-Meier method and Cox regression proportional hazard model between favorable and unfavorable risk groups. RESULTS: We identified a total of 123 CUP patients (n = 86 unfavorable, n = 37 favorable risk as per the 2023 ESMO guidelines). Sixty-four patients (52%) were assigned a tissue of origin by the treating clinician. Median progression free survival (PFS) was 6.8 (95% confidence interval (CI) 5.1-12.1) months and overall survival (OS) 10.2 (95% CI 6.0-18.5) months. Unfavorable risk (hazard ratio [HR] 2.9, p = 0.006), poor performance status (HR 2.8, p < 0.001), and non-squamous histology (HR 2.5, p < 0.05) were associated with poor survival outcome. A total of 70 patients (57%) proceeded to systemic therapy. In patients with non-squamous histology and unfavorable risk, site-specific therapy compared to empirical chemotherapy did not improve outcome (median OS 8.2 vs. 11.8 months, p = 0.7). CONCLUSIONS: In this real-world cohort, CUP presentations were heterogenous. Overall survival and rates of systemic treatment were poor. Poor performance status and unfavorable risk were associated with worse survival. For most patients, site-specific therapy did not improve survival outcome. Improved and timely access to diagnostic tests and therapeutics for this group of patients is urgently required.

Head and neck cancer of unknown primary: unveiling primary tumor sites through machine learning on DNA methylation profiles.

BACKGROUND: The unknown tissue of origin in head and neck cancer of unknown primary (hnCUP) leads to invasive diagnostic procedures and unspecific and potentially inefficient treatment options for patients. The most common histologic subtype, squamous cell carcinoma, can stem from various tumor primary sites, including the oral cavity, oropharynx, larynx, head and neck skin, lungs, and esophagus. DNA methylation profiles are highly tissue-specific and have been successfully used to classify tissue origin. We therefore developed a support vector machine (SVM) classifier trained with publicly available DNA methylation profiles of commonly cervically metastasizing squamous cell carcinomas (n = 1103) in order to identify the primary tissue of origin of our own cohort of squamous cell hnCUP patient's samples (n = 28). Methylation analysis was performed with Infinium MethylationEPIC v1.0 BeadChip by Illumina. RESULTS: The SVM algorithm achieved the highest overall accuracy of tested classifiers, with 87%. Squamous cell hnCUP samples on DNA methylation level resembled squamous cell carcinomas commonly metastasizing into cervical lymph nodes. The most frequently predicted cancer localization was the oral cavity in 11 cases (39%), followed by the oropharynx and larynx (both 7, 25%), skin (2, 7%), and esophagus (1, 4%). These frequencies concord with the expected distribution of lymph node metastases in epidemiological studies. CONCLUSIONS: On DNA methylation level, hnCUP is comparable to primary tumor tissue cancer types that commonly metastasize to cervical lymph nodes. Our SVM-based classifier can accurately predict these cancers' tissues of origin and could significantly reduce the invasiveness of hnCUP diagnostics and enable a more precise therapy after clinical validation.

Cancers of Unknown Primary Origin: Real-World Clinical Outcomes and Genomic Analysis at the European Institute of Oncology.

BACKGROUND: Cancer of unknown primary origin (CUP) poses a significant challenge due to poor clinical outcomes and limited treatment options. As such, further definition of clinicopathological factors and genomic profile to better adapt treatment strategies is required. METHODS: Medical records were interrogated to retrospectively include CUP with available clinical and genomics data at the European Institute of Oncology. Next-generation sequencing (NGS) included targeted panels. Statistical analyses were conducted with R Software 4.2.2. RESULTS: A total of 44 patients were included. With a median follow-up of 39.46 months (interquartile range [IQR] 35.98-47.41 months), median PFS (mPFS) to first-line regimen was 3.98 months (95% CI 3.22-5.98), with a clinical benefit rate of 26% (95% CI 14%-49%), and disease control rate (DCR) limited to 48.28%. Most patients (26 of 31, 83.87%) received platinum-doublet chemotherapy, with no statistically significant difference between first-line treatment regimens. Median OS (mOS) was 18.8 months (95% CI 12.3-39.9), with a 12-month OS rate of 66% (95% CI 50%-85%). All patients received comprehensive genomic profiling (CGP). For 11 patients, NGS was unsuccessful due to low sample quantity and/or quality. For the remaining, TP53 (n = 16, 48%) and KRAS (n = 10, 30%) represented the most altered (alt) genes. No microsatellite instability was observed (0 of 28), while 6 of 28 (21.43%) tumors carried high TMB (≥10 mutation per megabase). Eight of 33 tumors (24.2%) displayed at least one actionable alteration with potential clinical benefit according to ESCAT. Only 2 of them received targeted therapy matched to genomic alterations, with a combined mPFS of 2.63 months (95% CI 1.84-not evaluable) as third-line regimens. Six patients received anti-PD1/PD-L1 therapy, showing a meaningful mPFS of 13 months (95% CI 2.04-not evaluable). CONCLUSION: CUP exhibits poor prognosis with limited benefits from standard treatment regimens. A significant proportion of CUPs carry actionable alterations, underscoring the importance of genomic profiling to gather additional treatment opportunities. In addition, immunotherapy might represent a valuable treatment option for a subset of CUP. Finally, accurate definition of sequencing methods and platforms is crucial to overcome NGS failures.

PD-L1 expression and microsatellite instability (MSI) in cancer of unknown primary site.

BACKGROUND: Cancer of unknown primary site (CUP) is a heterogeneous group of tumors for which the origin remains unknown. Clinical outcomes might be influenced by regulatory processes in its microenvironment. Microsatellite instability (MSI) is a predictive biomarker for cancer immunotherapy and its status, as well as co-occurrence with PD-L1 expression, is poorly evaluated. We aim to evaluate the expression of PD-L1 and the status of MSI in CUP and their possible associations with clinical-pathological features. METHODS: The combined positive score (CPS) PD-L1 expression was evaluated by immunohistochemistry. MSI status was assessed using a hexa-plex marker panel by polymerase chain reaction followed by fragment analysis. RESULTS: Among the 166 cases, MSI analysis was conclusive in 120, with two cases being MSI positive (1.6%). PD-L1 expression was positive in 18.3% of 109 feasible cases. PD-L1 expression was significantly associated with non-visceral metastasis and a dominance of nodal metastasis. The median overall survival (mOS) was 3.7 (95% CI 1.6-5.8) months and patients who expressed PD-L1 achieved a better mOS compared to those who did not express PD-L1 (18.7 versus 3.0 months, p-value: < .001). ECOG-PS equal to or more than two and PD-L1 expression were independent prognostic factors in multivariate analysis (2.37 and 0.42, respectively). CONCLUSION: PD-L1 is expressed in a subset (1/5) of patients with CUP and associated with improved overall survival, while MSI is a rare event. There is a need to explore better the tumor microenvironment as well as the role of immunotherapy to change such a bad clinical outcome.

Utility of UV Signature Mutations in the Diagnostic Assessment of Metastatic Head and Neck Carcinomas of Unknown Primary.

BACKGROUND: Metastatic carcinoma of unknown primary origin to the head and neck lymph nodes (HNCUP) engenders unique diagnostic considerations. In many cases, the detection of a high-risk human papillomavirus (HR-HPV) unearths an occult oropharyngeal squamous cell carcinoma (SCC). In metastatic HR-HPV-independent carcinomas, other primary sites should be considered, including cutaneous malignancies that can mimic HR-HPV-associated SCC. In this context, ultraviolet (UV) signature mutations, defined as ≥ 60% C→T substitutions with ≥ 5% CC→TT substitutions at dipyrimidine sites, identified in tumors arising on sun exposed areas, are an attractive and underused tool in the setting of metastatic HNCUP. METHODS: A retrospective review of institutional records focused on cases of HR-HPV negative HNCUP was conducted. All cases were subjected to next generation sequencing analysis to assess UV signature mutations. RESULTS: We identified 14 HR-HPV negative metastatic HNCUP to either the cervical or parotid gland lymph nodes, of which, 11 (11/14, 79%) had UV signature mutations, including 4 (4/10, 40%) p16 positive cases. All UV signature mutation positive cases had at least one significant TP53 mutation and greater than 20 unique gene mutations. CONCLUSION: The management of metastatic cutaneous carcinomas significantly differs from other HNCUP especially metastatic HR-HPV-associated SCC; therefore, the observation of a high percentage of C→T with CC →TT substitutions should be routinely incorporated in next generation sequencing reports of HNCUP. UV mutational signatures testing is a robust diagnostic tool that can be utilized in daily clinical practice.

Advances in Cancer Research: Current and Future Diagnostic and Therapeutic Strategies.

Cancers of unknown primary (CUP) exhibit significant cellular heterogeneity and malignancy, which poses significant challenges for diagnosis and treatment. Recent years have seen deeper insights into the imaging, pathology, and genetic characteristics of CUP, driven by interdisciplinary collaboration and the evolution of diagnostic and therapeutic strategies. However, due to their insidious onset, lack of evidence-based medicine, and limited clinical understanding, diagnosing and treating CUP remain a significant challenge. To inspire more creative and fantastic research, herein, we report and highlight recent advances in the diagnosis and therapeutic strategies of CUP. Specifically, we discuss advanced diagnostic technologies, including 12-deoxy-2-[fluorine-18]fluoro-D-glucose integrated with computed tomography (18F-FDG PET/CT) or 68Ga-FAPI (fibroblast activation protein inhibitor) PET/CT, liquid biopsy, molecular diagnostics, self-assembling nanotechnology, and artificial intelligence (AI). In particular, the discussion will extend to the effective treatment techniques currently available, such as targeted therapies, immunotherapies, and bio-nanotechnology-based therapeutics. Finally, a novel perspective on the challenges and directions for future CUP diagnostic and therapeutic strategies is discussed.

Biomarkers of systemic inflammation provide additional prognostic stratification in cancers of unknown primary.

BACKGROUND: Biomarkers of systemic inflammation have been shown to predict outcomes in patients with cancer of unknown primary (CUP). We sought to validate these findings in patients with confirmed CUP (cCUP) and explore their role alongside existing clinicopathological prognostic categories. PATIENTS AND METHODS: CUP oncologist from across the United Kingdom were invited to include patients with cCUP referred to their local CUP multidisciplinary team. Patient demographics, clinical, pathological and outcome data were recorded and analysed. RESULTS: Data were available for 548 patients from four CUP services. 23% (n = 124) of patients met clinicopathological criteria for favourable-risk cCUP. On multivariate analysis c-reactive protein (CRP) (p < 0.001) and the Scottish Inflammatory Prognostic Score (SIPS: combining albumin and neutrophil count) (p < 0.001) were independently predictive of survival. CRP and SIPS effectively stratified survival in patients with both favourable-risk and poor-risk cCUP based on clinicopathological features. CONCLUSIONS: Biomarkers of systemic inflammation are reliable prognostic factors in patients with cCUP, regardless of clinicopathological subgroup. We recommend that CRP or SIPS are incorporated into routine clinical assessments of patients with cCUP as a tool to aid investigation and/or treatment decision-making across all groups. Established clinicopathological factors can then be used to inform management pathways and specific systemic anticancer therapy selection.

Bone metastatic cancer of unknown primary at initial presentation

Introduction Cancer of unknown primary (CUP) is a challenging malignancy. The purpose of this study was to investigate the clinical characteristics and prognosis of bone metastatic CUP using the population-based Surveillance, Epidemiology, and End Results (SEER) database. Methods From the SEER database, we identified 1908 patients with bone metastatic CUP at initial presentation between 2010 and 2018. Histology was subdivided following International Classification of Diseases for Oncology codes as Adenocarcinoma, Squamous cell, Neuroendocrine, or Carcinoma not otherwise specified (NOS). Cox proportional hazard modeling was applied using factors of age, sex, ethnicity, histological subtype, and therapeutic intervention. Results Among the 1908 patients, histology was Neuroendocrine in 240 patients, Squamous cell in 201 patients, Adenocarcinoma in 810 patients and NOS in 657 patients. In each subtype, patients tended to be predominantly male and white. Chemotherapy was introduced for 28% of patients and radiation for 34% in the entire cohort. Survival in patients with bone metastatic CUP was unfavorable, with a median survival of 2 months. Among the histological subtypes, Adenocarcinoma showed shorter survival than the other groups. In addition, treatment interventions such as chemotherapy and radiation therapy prolonged survival, particularly for Squamous cell, Adenocarcinoma and NOS, but not for Neuroendocrine. Discussion Bone metastatic CUP showed extremely poor prognosis, but treatment interventions such as chemotherapy and radiation generally offered survival benefits. Further randomized clinical research is needed to confirm the present results (AU)

Pelvic squamous cell carcinoma of unknown primary origin with hydronephrosis and ureteral stricture: A case report.

BACKGROUND: Cancer of unknown primary (CUP) is a very challenging disease, accounting for 2% to 9% of all new cancer cases. This type of tumor is a heterogeneous tumor whose primary site cannot be determined by standard examination. It has the characteristics of early metastasis, strong aggressiveness, and unpredictable mode of metastasis. Studies have shown that there is no consensus on the treatment of CUP and that there is a wide range of individual differences. In most cases, surgical removal of tumor is the most typical treatment for pelvic tumors. Herein, we report a case of a large pelvic tumor of unknown origin that had compressed the sigmoid colon and ureter and was completely removed by surgery. Postoperative diagnosis was pelvic metastatic squamous cell carcinoma. CASE SUMMARY: A 68-year-old man with pelvic tumor who initially complained of recurrent low back pain and painful urination. The mass was initially diagnosed as a pelvic tumor of unknown origin. The patient underwent complete resection of the tumor by laparotomy. The tumor was pathologically diagnosed as squamous cell carcinoma. CONCLUSION: Based on the treatment experience of this case, surgery alone cannot improve the poor prognosis of CUP. Since chemotherapy and immunotherapy have achieved promising efficacy in various cancers, and immunotherapy has the characteristics of low side effects and good tolerability, we recommend that patients with CUP should receive chemotherapy and/or immunotherapy for better survival outcomes.

Inguinal nodal metastatic squamous cell carcinoma of unknown primary (CUP) detected 7 years before the diagnosis of vulvar squamous cell carcinoma: A case report.

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. CASE REPORT: 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. CONCLUSION: 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.

Bone metastatic cancer of unknown primary at initial presentation.

INTRODUCTION: Cancer of unknown primary (CUP) is a challenging malignancy. The purpose of this study was to investigate the clinical characteristics and prognosis of bone metastatic CUP using the population-based Surveillance, Epidemiology, and End Results (SEER) database. METHODS: From the SEER database, we identified 1908 patients with bone metastatic CUP at initial presentation between 2010 and 2018. Histology was subdivided following International Classification of Diseases for Oncology codes as Adenocarcinoma, Squamous cell, Neuroendocrine, or Carcinoma not otherwise specified (NOS). Cox proportional hazard modeling was applied using factors of age, sex, ethnicity, histological subtype, and therapeutic intervention. RESULTS: Among the 1908 patients, histology was Neuroendocrine in 240 patients, Squamous cell in 201 patients, Adenocarcinoma in 810 patients and NOS in 657 patients. In each subtype, patients tended to be predominantly male and white. Chemotherapy was introduced for 28% of patients and radiation for 34% in the entire cohort. Survival in patients with bone metastatic CUP was unfavorable, with a median survival of 2 months. Among the histological subtypes, Adenocarcinoma showed shorter survival than the other groups. In addition, treatment interventions such as chemotherapy and radiation therapy prolonged survival, particularly for Squamous cell, Adenocarcinoma and NOS, but not for Neuroendocrine. DISCUSSION: Bone metastatic CUP showed extremely poor prognosis, but treatment interventions such as chemotherapy and radiation generally offered survival benefits. Further randomized clinical research is needed to confirm the present results.