Paraneoplastic symptom

Diagnosis Malignant tumour formation is accompanied by inappetence and weight loss, pain in the upper right abdominal quadrant, fever, specific laboratory findings and paraneoplastic symptoms, (see chapter 37)... 

Palliation of symptoms in nonoperable patients was also included in some outcome analyses. The details of symptoms and therapeutic effects of renal artery embolization are generally lacking, but studies generally reported thathematuria, pain, and paraneoplastic symptoms were alleviated. In one study, severe hematuria resolved in 11 of 14 patients, and incomplete embolization of the tumor blood supply from parasitized lumbar arteries resulted in persistent hematuria in 3 of 14 patients [11]. In another study, malignant hypercalcemia resolved after embolization [10]. Kalman and Varenhorst concluded that a small group of patients with specific, tumor-related symptoms may benefit from embolization. However, the palliative effect of embolization cannot be evaluated from the available data, and the effectiveness of the procedure awaits validation. 

The signs and symptoms of lung cancer can be classified as pulmonary, extrapulmonary, and paraneoplastic. These classifications relate to disease progression. 

Signs and symptoms of lung cancer can be classified into three subdivisions pulmonary, extrapulmonary, and paraneoplastic syndromes. Distinguishing between these classes of symptoms is important because it can aid in determining the severity of the disease, guide treatment options, and affect prognosis. 

Symptoms that are not a result of the direct effects of the tumor are termed paraneoplastic syndromes. They may be caused by substances secreted by the tumor or in response to the tumor and often occur in tissues far from the site of malignancy. Fhraneoplastic syndromes are numerous and affect a wide variety of systems, including the endocrine, neurologic, skeletal, renal, metabolic, vascular, and hematologic systems. 

Becldes MA, Spiro SG, Colice GL, et al. Initial evaluation of the patient with lung cancer Symptoms, signs, laboratory tests, and paraneoplastic syndromes. Chest 2003 123(1 suppl) 97S-104S. 

All patients must have a thorough history and physical examination to detect signs and symptoms of the primary tumor, regional spread of the tumor, distant metastases, paraneoplastic syndromes, and ability to withstand aggressive surgery or chemotherapy. 

Cancer patients often develop symptoms from organs remote from the primary tumor. The symptoms are usually caused by metastasis or toxic effects of therapy and less often by such secondary factors as nutritional deficiency, metabolic disturbances, opportunistic infections, and effects of critical illness. Other systemic diseases such as diabetes or amyloid may become manifest or aggravated during the course of the cancer disease and cause symptoms from remote organs. Paraneoplastic neurological syndromes (PNS) are a rare cause of remote symptoms [1]. The PNS affect less than 1% of all cancer patients [2], Even in small cell lung cancer (SCLC), the tumor type most commonly associated with PNS, these disorders occur in less than 5% of the patients [3, 4],... 

There are several individual and serial case reports of patients with tumors and extrapyramidal features such as chorea, ballistic movements, and dystonia [35, 63-65]. Again, SCLC is the most common associated tumor, but renal cancer and lymphoma are also reported [65]. Patients with Hu or Ma antibodies can exhibit extrapyramidal symptoms as part of the multifocal CNS involvement [65, 66], whereas CRMP-5 is probably the most common antibody associated with paraneoplastic chorea. Coexisting neuronal antibodies are found in 50% of the CRMP-5 positive cases, and accompanying symptoms such as vision loss, LE, loss of smell or taste, and peripheral neuropathy are often present [65]. Movement disorders are uncommon in CRMP-5 positive patients in general, being a clinical feature in only 15% (subacute chorea in 11%) [30]. In some patients, paraneoplastic causation is strongly suspected even when no known onconeural antibody is detected [64, 65]. Individual patients have shown clinical improvement and decline in antibody levels after chemotherapy or methylprednisolone [65, 67]. 

Paraneoplastic autonomic neuropathy is primarily seen with SCLC [103]. Lymphoma, non-small cell lung cancer, and ovarian cancer are also associated with autonomic disturbances [104]. Autonomic dysfunction affects 23-30% of Hu antibody positive patients [36, 98] and is the predominant symptom at presentation in up to 9% of the patients [90]. The onset of symptoms is usually subacute. A prominent clinical manifestation in patients with paraneoplastic autonomic neuropathy is gastrointestinal dysmotility and intestinal pseudo-obstruction, which can occur as part of the PEM/SN syndrome or as the sole symptom of Hu antibody related PNS. Ortostatic hypotension and erectile dysfunction are other common features [37, 105, 106], Autonomic neuropathy is also commonly associated with the CRMP-5 antibody and have been detected in more than 30% of CRMP-5 antibody positive patients [30], Inflammation in autonomic ganglia and infiltration of B and T cells have been demonstrated at autopsy [107], and Hu antibodies have been shown to induce neuronal apoptosis in cultured myenteric neurons [105],... 

Polyneuropathy with both sensory and motor involvement is much more common among cancer patients than pure SN [83, 110, 111]. SCLC is the most common associated tumor, although other solid tumors may be found [112]. Sensory-motor neuropathy is a quite common paraneoplastic feature in patients with onconeural antibodies, especially Hu and CRMP-5 antibodies. The CRMP-5 antibody is particularly associated with SCLC and thymoma [30]. The CRMP-5 antibody binds to oligodendrocytes as well as to neurons in specific brain regions and the retina and Schwann cells of the peripheral nervous system. In accordance with this, the clinical characteristics are heterogeneous. Many patients exhibit mixed axonal and demye-linating sensory-motor neuropathy, optic neuritis, or cerebellar dysfynction [85, 113], as well as extrapyramidal symptoms (Chapter 5.3). 

Neuromyotonia, or Isaacs syndrome, can occur as a paraneoplastic manifestation [138]. In a study of 60 patients with neuromyotonia, 8 individuals developed lung cancer or malignant lymphoma [139]. Importantly, and in contrast to most other PNS, the tumors presented after the symptoms of nerve hyperexitability, in some cases up to 4 years later. This long latency has also been reported in LEMS with SCLC [140]. 

Whereas idiopathic OM often resolves, spontaneously or after administration of intravenous immunoglobuline or corticosteroids [58], the outcome of paraneoplastic OM is more variable and depends on the tumor response to therapy. Children with paraneoplastic OM frequently respond to chemotherapy, adrenocorticotropic hormone, or immunomodulation [223], The response to immune therapy in adults with paraneoplastic OM is very modest, but prompt tumor therapy, immunomodulation, and depletion of IgG may be of some benefit [62, 224], Without antineoplastic therapy, the prognosis is usually poor, and symptoms often progress, ultimately causing death [62],... 

As a general rule, patients with PNS of the neuromuscular junction benefit considerably from cancer therapy. Immunotherapy of paraneoplastic LEMS, such as prednisone or plasmapheresis, can improve the symptoms for a while as the pathogenic VGCC antibodies are removed, but effective treatment of the underlying tumor is the cornerstone of therapy [201, 231],... 

Gultekin SH, Rosenfeld MR, Voltz R, Eichen J, Posner JB, Dalmau J. Paraneoplastic limbic encephalitis Neurological symptoms, immunological findings and tumour association in 50 patients. Brain 2000 123(Pt. 7) 1481-1494. 

Nagashima T, Mizutani Y, Kawahara H, Maguchi S, Terayama Y, Shinohara T, et al. Anti-Hu paraneoplastic syndrome presenting with brainstem-cerebellar symptoms and Lambert-Eaton myasthenic syndrome. Neuropathology 2003 23(3) 230-238. 

The paraneoplastic syndromes of the nervous system arise in association with a cancer (Darnell Posner, 2003). However, the neurological symptoms are characteristic of certain types of cancer and often precede the identification of the underlying malignancy. Therefore, proper identification of the neurological disorder will be of help in finding the cancer that causes the neurological disability. Most of these disorders are immune-mediated and characterized by the presence of autoantibodies. Sensory neuropathy and limbic... 

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