What are the key clinical features that may suggest a paraneoplastic syndrome in a patient with an undiagnosed malignancy?

Key clinical features that may suggest a paraneoplastic syndrome in a patient with an undiagnosed malignancy include a constellation of non-specific systemic symptoms and specific organ-related manifestations that are not directly caused by the primary tumour or its metastases. These features often precede the diagnosis of cancer and can involve multiple systems.

Systemic symptoms commonly observed are unexplained weight loss, persistent fatigue, fever, night sweats, and appetite loss or early satiety. These symptoms are frequently reported in various cancers such as lung, ovarian, pancreatic, and haematological malignancies and may prompt urgent investigation or referral ¹.

Haematological abnormalities such as unexplained anaemia (pallor), new onset diabetes with weight loss (suggestive of pancreatic cancer), deep vein thrombosis, and persistent or recurrent infections may also indicate an underlying malignancy with paraneoplastic phenomena ¹.

Neurological and rheumatological manifestations are hallmark features of paraneoplastic syndromes. These include inflammatory arthritis, myositis, neuropathies, and other autoimmune phenomena that arise due to immune cross-reactivity between tumour antigens and normal tissues (Leipe and Schulze-Koops, 2018). Such symptoms may present before the cancer is clinically apparent and should raise suspicion of a paraneoplastic syndrome.

Other clinical signs include unexplained lymphadenopathy or splenomegaly associated with night sweats or pruritus, which may suggest lymphoma or other haematological cancers ¹.

In summary, the presence of unexplained systemic symptoms (weight loss, fatigue, fever, night sweats), haematological abnormalities, thromboembolic events, and autoimmune or neurological symptoms should alert clinicians to the possibility of a paraneoplastic syndrome and prompt urgent cancer investigation and referral ¹ (Leipe and Schulze-Koops, 2018).