The symptomatic presentation in this case was atypical and misleading. The patient had a relatively healthy medical history and no family history of tumors. Her initial symptoms consisted of chest tightness and exertional dyspnea—both nonspecific and attributable to a wide range of etiologies. Potential causes include acute or chronic cardiopulmonary diseases, pulmonary tuberculosis, pleural effusion secondary to lung tumors, or other pleural pathologies. When assessing pulmonary or neoplastic conditions, possible extrathoracic malignancies must also be carefully considered. A comprehensive diagnostic evaluation should incorporate demographic factors such as gender and age, along with a detailed medical history.

This case illustrates considerable diagnostic difficulty. Ovarian neoplasms are especially prone to being overlooked due to overlapping and nonspecific symptoms. The atypical presentation seen here can readily lead to a missed diagnosis of ovarian cancer, misdirect clinical judgment, and ultimately delay appropriate treatment.

In this case, the patient showed a more pronounced elevation of amylase in the pleural fluid than in the serum or urine. Although elevated pleural fluid amylase is typically considered of pancreatic origin—since inflammation, tumors, or trauma can damage the pancreas or its ducts, leading to leakage of pancreatic fluid into the thoracic and abdominal cavities, which irritates the pleura and peritoneum and results in effusions—several findings argued against pancreatitis here. Notably, despite elevated pleural, serum, and urinary amylase, the more specific serum lipase was not increased, and the patient displayed no signs of an acute abdomen.

According to the Chinese Guidelines for the Diagnosis and Treatment of Acute Pancreatitis (2021) (8), acute pancreatitis requires at least two of the following:1) Persistent upper abdominal pain; 2) Serum lipase or amylase >3 times the upper limit of normal; 3) Imaging findings consistent with acute pancreatitis. The characteristic symptom is usually severe mid−epigastric pain radiating to the back (9). Based on the patient’s clinical presentation and imaging, acute or concurrent pancreatitis was considered unlikely. Therefore, the source of amylase elevation remained unclear. Subsequent staining of pleural effusion cells and ovarian tissue confirmed the diagnosis of high-grade serous adenocarcinoma of the ovary with thoracic metastasis. We thus speculate that the elevated amylase may originate from the ovarian tumor cells themselves.

According to relevant literature, amylase genes AMY1 (salivary-type) and AMY2 (pancreatic-type) are also expressed in the lungs, trachea, ovaries, fallopian tubes, and cervix. Damage, inflammation, or tumors in these organs may activate these genes, leading to amylase synthesis and its secretion into the blood or body fluids, thereby elevating amylase levels (10). Alternatively, elevated amylase could be related to a paraneoplastic mechanism. Certain tumors, including small cell lung cancer and ovarian cancer, are known to secrete atypical bioactive substances as part of a paraneoplastic syndrome (11, 12). The increase in amylase may thus result from abnormal tumor cell metabolism or activation of relevant signaling pathways. In addition, inflammatory factors within the tumor microenvironment might stimulate adjacent tissues—such as mesothelial cells—to release amylase, although this mechanism requires further validation. Other possible explanations include metastatic invasion of the pancreas or pancreatic duct by ovarian cancer, leading to pancreatic-type amylase release, or tumor compression of lymphatic or vascular structures causing local ischemia or inflammation that indirectly promotes amylase release. Currently, however, evidence from this case is insufficient to support these latter hypotheses.

This case differs from previously reported ovarian cancers associated with hyperamylasemia. Among the approximately eight publications retrieved to date, most cases presented with abdominal symptoms, and hyperamylasemia was identified during the differential diagnosis (Ref. 11–17). In contrast, the initial symptom in this case was chest tightness—an atypical manifestation of ovarian cancer—rather than common signs such as lower abdominal pain. Notably, the amylase level in pleural fluid was markedly elevated at 4,995 U/L, significantly higher than that in serum (343 U/L; reference range: 35–135 U/L) and urine (1,513 U/L; reference range: 0–1,200 U/L). Such an insidious presentation accompanied by non-specific laboratory abnormalities substantially increases the risk of diagnostic delay.

Moreover, the patient presented with a massive left-sided pleural effusion in which the amylase level was markedly higher than in the serum. Immunohistochemical analysis of pleural effusion cells indicated a high-grade serous adenocarcinoma of ovarian origin, supporting the hypothesis that amylase may be produced by the ovarian cancer cells themselves. Notably, the patient’s preoperative amylase elevation returned to the normal range four weeks after surgery, consistent with findings reported by Yang et al. (13). The underlying mechanisms, however, require further investigation.

Elevated amylase is not specific to pancreatic disease. Besides acute or chronic pancreatitis, gallstones, cholangitis, intestinal perforation, or obstruction, hyperamylasemia has also been documented in multiple organ failure and diabetic ketoacidosis (14). Therefore, during differential diagnosis, the possibility of concurrent conditions contributing to amylase elevation should be carefully considered.

Currently, elevated amylase is not a routine diagnostic marker for ovarian cancer. However, an abnormal elevation may suggest an occult tumor, especially when accompanied by pleural or abdominal effusions. Although isolated cases have reported a link between ovarian cancer and increased serum amylase, large-scale clinical studies supporting this association are lacking (15).The mechanism behind amylase elevation in ovarian cancer may involve direct tumor secretion, paraneoplastic syndrome, or local microenvironmental changes. Nevertheless, the specific molecular pathways remain unclear and warrant further investigation.

The role of amylase as a potential tumor marker remains controversial. Elevated blood amylase has also been documented in myeloma, gastric cancer, lung cancer, and pheochromocytoma (16, 17), but the evidence mainly relies on case reports rather than large-scale studies. More extensive data are needed to clarify the specificity of amylase elevation and its relationship with tumor stage and pathological subtype. Future research could apply single-cell sequencing or proteomic technologies to elucidate the regulatory mechanisms of amylase gene expression in ovarian cancer cells. Meanwhile, multicenter studies should analyze both the incidence and prognostic significance of hyperamylasemia in ovarian cancer patients. Combining amylase with other established tumor markers (e.g., CA125 and HE4) may enable a more comprehensive clinical evaluation, particularly for early diagnosis and treatment monitoring.

This study has several limitations due to its retrospective design. Most notably, we lacked multi-site tissue sampling (e.g., from pancreas or parotid gland) and did not perform amylase isoenzyme typing. Pancreatic amylase is chiefly produced by pancreatic acinar cells, whereas salivary amylase has broader sources, including salivary glands, lungs, fallopian tubes, and certain tumors. Isoenzyme typing helps distinguish between pancreatic and salivary origins, thereby narrowing the diagnostic possibilities and improving specificity. Future studies should consider multi-site sampling and isoenzyme analysis to facilitate earlier differential diagnosis.