Paraneoplastic Syndromes Associated With MCC
Other paraneoplastic syndromes have been reported in association with MCC. A patient with brainstem encephalitis associated with MCC was reported in a trial of a novel immunotherapy for paraneoplastic neurologic syndromes.16,17 A syndrome of inappropriate antidiuretic hormone (SIADH) secretion was reported in a patient with N-type calcium channel antibodies.18 Two cases of paraneoplastic cerebellar degeneration have been reported; the first was associated with a novel 70-kD antibody,19 and the second was associated with the P/Q-type VGCC antibody.20 Anti-Hu antibodies have been found in a handful of reports of neurologic deterioration in patients with MCC. Hocar et al21 reported a severe necrotizing myopathy; Greenlee et al22 described a syndrome of progressive sensorimotor and autonomic neuropathy with encephalopathy; and Lopez et al23 described a constellation of vision changes, gait imbalance, and proximal weakness. Support for a pathophysiologic connection among these 3 cases is suggested by the finding of Hu antigen expression by MCC in 2 studies.24,25 Because MCC can present with occult lymph node involvement in the absence of primary cutaneous findings,3 there are more cases of paraneoplastic neurologic syndromes that were not recognized.
Extrapulmonary small cell carcinomas such as MCC are morphologically indistinguishable from their pulmonary counterparts and have been reported in most anatomic regions of the body, including gynecologic organs (eg, ovaries, cervix), genitourinary organs (eg, bladder, prostate), the gastrointestinal tract (eg, esophagus), skin (eg, MCC), and the head and neck region. Extrapulmonary small cell carcinoma is a rare entity, with the most common form found in the gynecologic tract, representing only 2% of gynecologic malignancies.26
Paraneoplastic syndromes of EPSCC are rare given the paucity of the malignancy. Several case reports discuss findings of SIADH in EPSCC of the cervix, as well as hypercalcemia, polyneuropathy, Cushing syndrome, limbic encephalitis, and peripheral neuropathy in EPSCC of the prostate.27,28 In contrast, SCLC has long been associated with paraneoplastic syndromes. Numerous case reports have been published describing SCLC-associated paraneoplastic syndromes to include hypercalcemia, Cushing syndrome, SIADH, vasoactive peptide production, cerebellar degeneration, limbic encephalitis, visceral plexopathy, autonomic dysfunction, and LEMS.29 As more cases of EPSCC with paraneoplastic syndromes are identified and reported, we might gain a better understanding of this interesting phenomenon.
Conclusion
Merkel cell carcinoma is an aggressive neuroendocrine malignancy associated with paraneoplastic neurologic syndromes, including LEMS. A thorough search for an underlying malignancy is highly recommended in patients with diagnosed LEMS without clear cause. Early identification and treatment of the primary tumor can lead to improvement of neurologic symptoms.
We present a case of LEMS with no clearly identifiable cause on presentation with later diagnosis of metastatic MCC of unknown primary origin. After surgical excision of affected lymph nodes and adjuvant radiation therapy, the patient had near-complete resolution of LEMS symptoms at 6-month follow-up, without additional findings of lymphadenopathy or skin lesions. Although this patient is not undergoing routine surveillance imaging to monitor for recurrence of MCC, a chest CT or positron emission tomography–CT for secondary screening would be considered if the patient experienced clinical symptoms consistent with LEMS.
In cases of LEMS without pulmonary malignancy, we recommend considering MCC in the differential diagnosis during the workup of an underlying malignancy