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It is generally accepted that Lambert-Eaton myasthenic syndrome (LEMS) is associated with cancer in 50% to 60% of cases, the overwhelming majority of these cancers being small cell carcinomas of the lung. O’Neill et al 1stated that in cases in which the cancer is not small cell carcinoma of the lung the association may be fortuitous. However, small cell carcinomas can sometimes arise in other organ systems. They are considered, like small cell carcinomas of the lung, to be of neuroendocrine origin and presumably have the same antigenic potential. Posner2 states that occasional cases of LEMS can be seen in association with non-pulmonary small cell carcinoma, particularly of the prostate and cervix, although reference to these occurrences in the literature is scant. We present a case of LEMS clearly causally related to extrapulmonary small cell carcinoma.
A 70 year old housewife presented in April 1996 with a three month history of leg weakness and dryness of the mouth. She was otherwise well. Examination disclosed quite pronounced weakness of hip flexion and mild weakness of knee extension and arm abduction. Deep tendon reflexes were all intact and did not become brisker after exercise. Her creatine phosphokinase concentration was normal. Electrical studies disclosed a compound muscle action potential of 3.5 mV in abductor digiti minimi on supramaximal stimulation of the right ulnar nerve at the wrist, increasing in amplitude by 40% after 20 seconds of isometric exercise. A voltage gated calcium channel antibody assay revealed a titre of 410 pM (>100 pM positive), confirming the presence of LEMS.
The patient was a lifelong non-smoker. There were no respiratory symptoms and a CT of her chest and bronchoscopy were normal. It was considered that she probably had LEMS unrelated to underlying malignancy.
Three months after presentation, she complained of a swollen right leg and a mass was palpable in the right inguinal region. A biopsy of this disclosed small cell carcinoma. Investigations to discover a source for this tumour included CT of the abdomen and pelvis, a bronchoscopy with bronchial washings, a gynaecological examination with cervical and endocervical cytology, urine cytology, and upper gastrointestinal endoscopy with oesophageal biopsy. No source of a primary tumour was detected. The patient was treated with combined local radiotherapy and chemotherapy, utilising two courses of cisplatin and etoposide followed by three courses of cyclophosphamide and doxorubicin. The inguinal mass rapidly shrank after this treatment and by November 1996 had clinically and radiologically resolved. The patient no longer complained of xerostomia and thought that her strength was almost normal. Her deep tendon reflexes were all very brisk, certainly brisker than when she first presented six months previously, but there was some residual weakness of hip flexion. Ten months after her initial presentation, her voltage gated calcium channel antibody assay was negative. Fifteen months after presentation there was no clinical or radiological evidence of recurrent tumour. The only abnormal finding on examination was persisting mild weakness of hip flexion. Electrical studies disclosed a compound muscle action potential of 6.7 mV in Abductor digiti minimi on supramaximal stimulation of the right ulnar nerve at the wrist, with no significant increment in amplitude following 20 seconds of isometric contraction.
Despite intensive investigations, no primary source for our patient’s small cell carcinoma was found. It is unlikely that this patient has a primary lung cancer: she is a lifelong non-smoker, the chest investigations were all negative, and inguinal nodes would be a most unusual site for metastatic lung disease to first appear. Small cell carcinoma of the cervix, probably the next most common primary small cell carcinoma, also seems unlikely in view of her negative gynaecological findings. It is possible that her presenting tumour represents metastasis from an occult primary abdominal neoplasm, such as pancreatic or colonic cancer. We think that this patient had LEMS causally related to non-pulmonary small cell carcinoma of unknown origin. The clinical, electrical, and immunological findings were identical to those of LEMS associated with small cell carcinomas of the lung. It is likely that the immunological stimulus for the development of LEMS is the same in this case as in cases associated with small cell carcinomas of the lung. Standard chemotherapeutic treatment for small cell carcinoma has resulted in complete clinical and radiological resolution of her tumour and resolution of the clinical, electrical, and immunological features of her LEMS. It remains to be seen whether this is only a remission.
We thank the Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, for performing the voltage gated calcium channel antibody assays.