Comment
Carcinoid tumors are uncommon neoplasms of neuroendocrine origin that generally arise in the gastrointestinal or bronchopulmonary tracts. Metastases from these primary neoplasms more commonly affect the regional lymph nodes or viscera, with rare reports of cutaneous metastases to the skin. The true incidence of carcinoid tumors with metastasis to the skin is unknown because it is limited to single case reports in the literature.
The clinical presentation of cutaneous carcinoid metastases has been reported most commonly as firm papules of varying sizes with no specific site predilection.1 The color of these lesions has ranged from erythematous to violaceous to brown.2 Several of the reported cases were noted to be extremely tender and painful, while other reports of lesions were noted to be asymptomatic or only mildly pruritic.3-7
Carcinoid syndrome is more common with neoplasms present within the gastrointestinal tract, but it also has been reported with large bronchial carcinoid tumors and with metastatic disease.8,9 Paroxysmal flushing is the most prominent cutaneous manifestation of this syndrome, occurring in 75% of patients.10,11 Other common symptoms include patchy cyanosis, telangiectasia, and pellagralike skin lesions.3 Carcinoid syndrome secondary to bronchial adenomas is thought to differ from gastrointestinal carcinoid neoplasms in that it has prolonged flushing (hours to days instead of minutes) and is characterized by marked anxiety, fever, disorientation, sweating, and lacrimation.8,9
Many cases of cutaneous carcinoid metastases have been accompanied by reports of exquisite tenderness,7 similar to our patient. The pathogenesis of the pain in these lesions is still unclear, but several hypotheses have been established. It has been postulated that perineural invasion by the tumor is responsible for the pain; however, this finding has been inconsistent, as neural involvement also has been present in nonpainful lesions.2,5,7,12 Another theory for the pain is that it is secondary to the release of vasoactive substances and peptide hormones from the carcinoid cells, such as kallikrein and serotonin. Lastly, local tissue necrosis and fibrosis also have been suggested as possible etiologies.7
The histology of cutaneous carcinoid metastases typically resembles the primary lesion and may demonstrate fascicles of spindle cells with focal areas of necrosis, mild atypia, and a relatively low mitotic rate.10 Other neoplasms such as Merkel cell carcinoma and carcinoidlike sebaceous carcinoma should be considered in the differential diagnosis. A primary malignant peripheral primitive neuroectodermal tumor or a primary cutaneous carcinoid tumor is less common but should be considered. Differing from carcinoid tumors, Merkel cell carcinomas usually have a higher mitotic rate and positive staining for CK20. The sebaceous neoplasms with a carcinoidlike pattern may appear histologically similar, requiring immunohistochemical evaluation with monoclonal antibodies such as D2-40.13 A diffuse granular cytoplasmic reaction to chromogranin A is characteristic of carcinoid tumors. Synaptophysin and TTF-1 also are positive in carcinoid tumors, with TTF-1 being highly specific for neuroendocrine tumors of the lung.10
Cutaneous metastases of internal malignancies are more common from carcinomas of the lungs, gastrointestinal tract, and breasts.5 Occasionally, the cutaneous metastasis will develop directly over the underlying malignancy. Our case of cutaneous metastasis of a carcinoid tumor presented as an exquisitely tender and painful papule on the cheek. The histology of the lesion was consistent with the known carcinoid tumor of the lung. Because these lesions are extremely uncommon, it is imperative to obtain an accurate clinical history and use the appropriate immunohistochemical panel to correctly diagnose these metastases.