Final diagnosis of malignancy and clinical features of patients presenting with metastases

Authors

Abstract

AimDiagnosing the primary cancer can be difficult in patients whose first symptom is metastasis. This research sought to explore key characteristics and potential indicators for identifying primary cancer in patients with metastasis.
MethodsIn this retrospective study, 280 patients with no known cancer who were hospitalized in the Internal Medicine Clinic of our hospital with the finding of metastasis were included. Admission symptoms and findings, clinical status, comorbidities, laboratory parameters, imaging findings, and the final diagnosis of malignancy were recorded and analyzed. The characteristics of the patients were compared according to the cancer type.
ResultsAmong the patients, 112 were female, and 168 were male. The most common malignancies diagnosed were lung cancer (64 patients), gastric cancer (39 patients), colorectal cancer (37 patients), and pancreatic cancer (37 patients). When the most common malignancies were compared with other malignancies, associated parameters for lung cancer were found to be smoking, hemoglobin, shortness of breath, presence of brain metastasis, and absence of diabetes (p<0.05). Significant parameters associated with gastric cancer were low hemoglobin, mean corpuscular volume (MCV), albumin, sodium value, and weight loss (p<0.05). Significant parameters associated with colorectal cancer were MCV, liver metastasis, and gastrointestinal bleeding (p<0.05).
ConclusionIn patients with evidence of metastases, the parameters associated with lung cancer are smoking, hemoglobin level, dyspnea, brain metastases, and absence of diabetes. Low hemoglobin, low MCV, low albumin, and weight loss suggest the diagnosis of gastric cancer. Colorectal cancer should be considered in patients with liver metastases and gastrointestinal bleeding.

Keywords

Introduction

Cancer is one of the most important causes of death in the world.¹The prolonged life expectancy and the proportion of the elderly population increase the incidence of cancer.^1,2Early diagnosis of cancer and identification of people at risk are important for cancer prevention. However, cancer can sometimes present at an advanced stage with signs of metastasis.³ Clinical presentation in metastatic malignancies varies according to the characteristics of the primary tumor and metastasis. Systemic symptoms, including weight loss, anorexia, weakness, pain, night sweats, and sub-febrile fever, are common findings.⁴ Patients may also present with skeletal pain, pathologic fractures, confusion, constipation, dyspnea, cough, headache, focal neurologic deficits, seizures, and hemoptysis.⁵
In patients presenting with signs and symptoms of metastasis, diagnosing primary malignancy as soon as possible and initiating appropriate treatment is very important in preventing complications and improving patient survival.^3,6 However, it may sometimes be difficult and time-consuming to make a pathological diagnosis of cancer.^5,6,7,8,9 This research sought to explore key characteristics and potential indicators for identifying primary cancer in patients with presenting metastasis.

Materials and Methods

In this retrospective study, consecutive patients without any pathologically known malignancy diagnosis who were hospitalized in the Internal Medicine Clinic of Sakarya Training and Research Hospital between June 2020 and October 2023 due to signs or symptoms of metastasis were included. Inclusion criteria were that the patients had no known diagnosis of cancer, were 18 years of age or older, and were hospitalized. Patients under 18 years of age, patients with a known diagnosis of malignancy, patients with insufficient or incomplete data, and patients with no pathologic diagnosis were excluded from the study.
Demographic data, admission symptoms and findings, comorbidities, laboratory parameters, radiologic findings, metastasis regions, and final pathologic malignancy diagnoses were recorded. Data were obtained from the hospital registration system. Patients were divided into groups according to cancer types, and a specific cancer group was compared with other cancer groups. The study aimed to determine possible discriminative factors for the most common cancer diagnoses.
Ethical ApprovalThe study was approved by the Ethics Committee of Sakarya University, School of Medicine (Date: 26.12.2022, Decision No: E2-22-2376: 71522473-050.01.04-113305-355).
Statistical AnalysisSPSS (Statistical Package for Social Sciences) for Windows 23.0 software was used for statistical analysis of the data. Data distribution was analyzed using the Kolmogorov-Smirnov test. Continuous variables were expressed as mean ± standard deviation or median (25th percentile - 75th percentile); categorical variables were expressed as number of cases (n) and percentage (%). The Mann–Whitney test was used for non-parametric data. Student’s t-test was used to examine the difference between means. Pearson's chi-square test or Fisher's Chi-square test with Fisher's exact test were used for comparative analysis of qualitative variables. The associated variables for malignancy diagnoses were performed by Binary logistic regression analysis. Statistical significance was accepted as a P-value <0.05.
Reporting GuidelinesThis study is reported in accordance with the STROBE guidelines for observational studies.

Results

Of the 280 patients included in the study, 40% (n = 112) were female, 60% (n = 168) were male, and the mean age was 66.3 ± 11 years. The comorbidities included hypertension in 120 (42.9%), diabetes in 69 (24.6%), coronary artery disease in 44 (15.7%), and heart failure in 15 (5.3%). Of the patients, 153 (54.6%) smoked, and 20 (7.1%) used alcohol. As a result of evaluations, 64 patients had lung cancer, 39 patients had gastric cancer, 37 patients had colorectal cancer, 37 patients had pancreatic cancer, 23 patients had ovarian cancer, 20 patients had cholangiocellular cancer, 13 patients had hepatocellular cancer, 12 patients had breast cancer, 8 patients had prostate cancer, 7 patients had renal cell carcinoma, 3 patients were diagnosed with malignant mesothelioma, 3 with urothelial cancer, 3 with esophageal cancer, 2 with endometrial cancer, 2 with malignant melanoma, 2 with laryngeal cancer, 1 with testicular cancer, 1 with synovial sarcoma, 1 with tonsil cancer, 1 with primary mesenchymal cancer of the liver and 1 with gallbladder cancer.
Of the patients, 103 had abdominal pain, 73 had weakness, 70 had weight loss, 55 had loss of appetite, 47 had nausea and vomiting, 42 had swelling, 21 had shortness of breath, 17 had jaundice, 12 had bleeding, 12 had constipation, 8 presented with cough, 8 with impaired consciousness, 5 with headache, 5 with chest pain, 4 with night sweats, 4 with palpable mass, 3 with visual disturbance, 1 with hemoptysis and 62 with other signs and symptoms. Liver metastases were present in 111 patients, lymph node metastases in 105, bone and lung metastases in 19, brain metastases in 14, and metastases to other rare sites in 12.
The data of patients with lung cancer and patients with other cancers were shown in Supplementary Table 1. The parameters associated with lung cancer were shown in Supplementary Table 2. The overall accuracy of lung cancer in this model, analyzed by logistic regression, was 84.9%. Thirty-nine patients (13.9%) were diagnosed with gastric cancer. There was no difference between patients with gastric cancer and patients with other cancers in terms of age, gender, smoking, and alcohol use (all p>0.05). Hemoglobin, mean corpuscular volume (MCV), iron, ferritin, albumin, alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT), and lactate dehydrogenase (LDH) were significantly lower in patients with gastric cancer compared to those without gastric cancer (all p<0.05). According to the logistic regression analysis, weight loss, hemoglobin, MCV, globulin, and serum sodium values were found to be significant for gastric cancer (all p<0.05). The overall accuracy of the model for gastric cancer was 86.8%.
Colorectal cancer was diagnosed in 37 patients (13.2%). There was no significant difference between patients with colorectal cancer and patients with other cancers in terms of age and gender (all p>0.05). Gastrointestinal bleeding and liver metastases were significantly higher in patients with colorectal cancer compared to other cancers (p<0.05 in all). In addition, ferritin, hemoglobin, and MCV values were significantly lower in patients with colorectal cancer (all p<0.05). On the other hand, carcinoembryonic antigen (CEA) was significantly higher in patients with colorectal cancer, while cancer antigen 15-3 and cancer antigen 125 were higher in patients without colorectal cancer (all p<0.05). According to logistic regression analysis to determine the parameters associated with colorectal cancers, MCV, liver metastasis, and gastrointestinal bleeding were found to be significant (p<0.05). The model's overall accuracy for colorectal cancer was 86.8%.

Discussion

Cancer patients may present with a broad spectrum of clinical signs and symptoms.¹⁰ Most of the time, the data at the time of initial presentation are insufficient for diagnosing malignancy.¹⁰ For example, when patients are diagnosed with lung cancer, they are often at an advanced stage, and this increases mortality. In a study including 698 lung cancer patients, hemoptysis, cough, auscultation findings in the lung, bone and back pain, weight loss, and fatigue were reported to be associated with lung cancer.¹¹ Patients may rarely present with paraneoplastic syndromes.¹¹ In our study, similar to this information, cough and shortness of breath were found to be significantly more common in patients with lung cancer than in patients with other cancers. In addition, impaired consciousness was also found to be significantly more common in patients with lung cancer. The cause of impaired consciousness was secondary to brain metastasis in most patients. The brain is one of the most common sites of metastasis in lung cancer.¹² In some studies, lung cancer was reported to be the etiology in approximately half of the patients with brain metastases.^13,14 The current study detected brain metastasis in 14 of 280 patients at initial presentation. Among these, 13 of 14 patients were diagnosed with lung cancer.
In the current study, male gender and smoking were found to be significant parameters in patients with lung cancer. Similarly, male gender and smoking have been reported to be significantly associated with lung cancer in previous studies on the subject.¹⁵ According to the current study, the probability of lung cancer was found to be 9.8 times higher in patients with dyspnea compared to patients without dyspnea. In addition, patients with impaired consciousness were 8.4 times more likely to have lung cancer than those without. Other parameters associated with lung cancer were smoking, the presence of brain metastasis, hemoglobin level, and the absence of diabetes.
Gastric cancer may also present with different signs and symptoms.¹⁶ In our study, hemoglobin, MCV, iron, and ferritin values were significantly lower in patients with gastric cancer than in those with other cancers. In the onset or course of gastric cancer, iron deficiency anemia may be observed due to both bleeding and malabsorption.¹⁶ In a study including 126 gastric cancer patients, iron deficiency anemia was reported in 40% of patients.¹⁷ In addition, in our study, weight loss and low albumin levels were found to be significant in patients with gastric cancer compared to patients with other cancers. The stomach is one of the most important organs for nutrition and digestion; therefore, more malnutrition may explain this result.^18,19 According to our study, patients presenting with metastasis and weight loss are 3 times more likely to have gastric cancer than those without weight loss.
Based on our study results, ALT, GGT, and LDH values were significantly higher in patients with metastatic cancer other than gastric cancer. The common feature of these enzymes is that they increase in liver pathologies. Hepatocellular carcinoma or liver metastasis may increase these enzymes.¹⁰ In the present study, weight loss, hemoglobin, MCV, globulin, and serum sodium values were found to have significant effects on gastric cancer in patients presenting with signs of metastasis.
Current study results demonstrated that gastrointestinal bleeding, liver metastasis, hemoglobin, MCV, ferritin, and ferritin levels were significantly lower in patients with colorectal cancer compared to patients with other cancers. In addition, when compared in terms of tumor markers, CEA was significantly higher in patients with colorectal cancer. In some previous studies, rectal bleeding, anorexia, abdominal pain, iron deficiency anemia, and changes in bowel habits were reported as the most common presenting symptoms of colorectal cancer.²⁰ Our research findings showed that MCV value, presence of liver metastasis, and gastrointestinal tract bleeding were found to have significant effects for the diagnosis of colorectal cancer.

Limitations

One of the limitations of the study is its retrospective design. Another limitation is that the patient data were collected from a single center, and the study population was relatively small.

Conclusion

According to current study findings, discriminative parameters for lung cancer in patients with metastasis findings without a diagnosis of cancer are smoking, hemoglobin value, shortness of breath, brain metastasis, and absence of diabetes. Low hemoglobin, low MCV, low albumin, and weight loss are associated with stomach cancer. Colorectal cancer should be considered in patients with low MCV, liver metastases, and gastrointestinal bleeding. These findings suggest that certain clinical and laboratory parameters may be associated with specific primary malignancies in patients presenting with metastases without a known cancer diagnosis.

Declarations

Abbreviations

ALT: Alanine aminotransferase
ANCOVA: Analysis of covariance
CEA: Carcinoembryonic antigen
CT: Computed tomography
GGT: Gamma-glutamyl transferase
LDH: Lactate dehydrogenase
MCV: Mean corpuscular volume
SPSS: Statistical package for social sciences
STROBE: Strengthening the reporting of observational studies in epidemiology

References

1. Siegel RL, Giaquinto AN, Jemal A. Cancer statistics, 2024. CA Cancer J Clin. 2024;74(1):12-49. doi:10.3322/caac.21820
   Article PubMed Google Scholar
2. Santucci C, Carioli G, Bertuccio P, et al. Progress in cancer mortality, incidence, and survival: a global overview. Eur J Cancer Prev. 2020;29(5):367-381. doi:10.1097/cej.0000000000000594
   Article PubMed Google Scholar
3. Lehrer EJ, Stoltzfus KC, Jones BM, et al. Trends in diagnosis and treatment of metastatic cancer in the United States. Am J Clin Oncol. 2021;44(11):572-579. doi:10.1097/coc.0000000000000866
   Article PubMed Google Scholar
4. Majidpoor J, Mortezaee K. Steps in metastasis: an updated review. Med Oncol. 2021;38(1):3. doi:10.1007/s12032-020-01447-w
   Article PubMed Google Scholar
5. Hanahan D. Hallmarks of cancer: new dimensions. Cancer Discov. 2022;12(1):31-46. doi:10.1158/2159-8290.cd-21-1059
   Article PubMed Google Scholar
6. Niu Y, Lin Y, Pang H, et al. Risk factors for bone metastasis in patients with primary lung cancer: a systematic review. Medicine (Baltimore). 2019;98(3):e14084. doi:10.1097/md.0000000000014084
   Article PubMed Google Scholar
7. DeVita VT, Lawrence TS, Rosenberg SA. Cancer: principles and practice of oncology primer of molecular biology in cancer. Philadelphia: Wolters Kluwer Health; 2020.
   PubMed Google Scholar
8. Gaddey HL, Riegel AM. Unexplained lymphadenopathy: evaluation and differential diagnosis. Am Fam Physician. 2016;94(11):896-903.
   PubMed Google Scholar
9. Coleman RE. Clinical features of metastatic bone disease and risk of skeletal morbidity. Clin Cancer Res. 2006;12(20):6243S-6249S. doi:10.1158/1078-0432.ccr-06-0931
   Article PubMed Google Scholar
10. Zakkak N, Barclay ME, Swann R, et al. The presenting symptom signatures of incident cancer: evidence from the English 2018 National Cancer Diagnosis Audit. Br J Cancer. 2024;130(2):297-307. doi:10.1038/s41416-023-02507-4
    Article PubMed Google Scholar
11. Prado MG, Kessler LG, Au MA, et al. Symptoms and signs of lung cancer prior to diagnosis: case-control study using electronic health records from ambulatory care within a large US-based tertiary care centre. BMJ Open. 2023;13(4):e068832. doi:10.1136/bmjopen-2022-068832
    Article PubMed Google Scholar
12. Riihimäki M, Hemminki A, Fallah M, et al. Metastatic sites and survival in lung cancer. Lung Cancer. 2014;86(1):78-84. doi:10.1016/j.lungcan.2014.07.020
    Article PubMed Google Scholar
13. Lamba N, Wen PY, Aizer AA. Epidemiology of brain metastases and leptomeningeal disease. Neuro Oncol. 2021;23(9):1447-1456. doi:10.1093/neuonc/noab101
    Article PubMed Google Scholar
14. Schroeder T, Bittrich P, Kuhne JF, et al. Mapping distribution of brain metastases: does the primary tumor matter? J Neurooncol. 2020;147(1):229-235. doi:10.1007/s11060-020-03419-6
    Article PubMed Google Scholar
15. Liang X, Gao X, Wang F, et al. Clinical characteristics and prognostic analysis of SMARCA4-deficient non-small cell lung cancer. Cancer Med. 2023;12(13):14171-14182. doi:10.1002/cam4.6083
    Article PubMed Google Scholar
16. Huang XZ, Yang YC, Chen Y, et al. Preoperative anemia or low hemoglobin predicts poor prognosis in gastric cancer patients: a meta-analysis. Dis Markers. 2019;2019:7606128. doi:10.1155/2019/7606128
    Article PubMed Google Scholar
17. Tang GH, Hart R, Sholzberg M, Brezden-Masley C. Iron deficiency anemia in gastric cancer: a Canadian retrospective review. Eur J Gastroenterol Hepatol. 2018;30(12):1497-1501. doi:10.1097/meg.0000000000001251
    Article PubMed Google Scholar
18. Crew KD, Neugut AI. Epidemiology of gastric cancer. World J Gastroenterol. 2006;12(3):354-362. doi:10.3748/wjg.v12.i3.354
    Article PubMed Google Scholar
19. Mott T, Gray C. Gastric cancer: rapid evidence review. Am Fam Physician. 2025;111(2):140-145.
    PubMed Google Scholar
20. Saraiva MR, Rosa I, Claro I. Early-onset colorectal cancer: a review of current knowledge. World J Gastroenterol. 2023;29(8):1289-1303. doi:10.3748/wjg.v29.i8.1289
    Article PubMed Google Scholar

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About This Article

Received:

March 18, 2026

Accepted:

May 14, 2026

Published Online:

May 14, 2026