Carcinoid tumors are neuroendocrine tumors derived from enterochromaffin cells, which are widely distributed in the body. They include less than 1% of all cancers and are most commonly found in the gastrointestinal tract and the bronchopulmonary system. Cutaneous involvement of carcinoid tumors is relatively rare, and carcinoid metastases to the skin and subcutaneous tissues are considered late manifestations of the disease.[1-3]
The diagnosis of skin metastasis from carcinoid tumor may be difficult, especially for dermatopathologists who are not familiar with carcinoid tumors.
A 43-year-old Caucasian woman presented to our institute with a 8-month history of a nodular lesion on her forehead that had slowly grown. The lesion appeared red-purplish, ranged 1.5 cm × 1 cm in diameter and was intensely painful (Fig. 1a).
The patient had a history of pulmonary atypical carcinoid tumor with metastatic hilar lymph node (pT3N1). The pulmonary tumor showed a trabecular pattern, with 6 mitoses/mm2 and foci of necrosis. The neoplasm was positive for neuroendocrine markers such as chromogranin, synaptophysin, CD57, CD56 and TTF1.
The histological examination of the cutaneous lesion showed a dermal and ipodermal proliferation, not localized, constituted by atypical epithelioid medium cells. The tumoral population was arranged as cords, with trabecular pattern (Fig. 1b). Cytologically, the cells were oval to polygonal with eosinophilic cytoplasm and hyperchromatic nuclei (Fig. 2a).
Immunohistochemical studies showed that the tumor cells were reactive for chromogranin (Fig. 2b), TTF1, cytokeratin (CK)7, synaptophysin, neuron-specific enolase, focally positive for CD56 (Fig. 2c) and negative for S100 protein and CK20 (Fig. 2d).
Based on the patient's history and scalp biopsy, a final diagnosis of skin metastasis of pulmonary atypical carcinoid tumor was made.
Cutaneous metastases (CM) occur in 0.7–9% of all patients with internal malignancies and metastatic tumor from carcinoid tumors represent an even smaller subset. Although visceral metastases of carcinoid tumors are common, CM are rare, and most CM are of bronchial origin.[1-3]
Cutaneous metastases tend to occur on the upper extremities, but can be found anywhere in the skin. CM are often painful and the pain is secondary to perineural invasion or to the release of vasoactive substances and peptide hormones, such as kallikrein and serotonin by carcinoid cells.[1-3] In our patient, we have assumed that the pain was closely related to perineural invasion.
The differential diagnosis included primary neuroendocrine tumor (primary cutaneous carcinoid or primary Merkel cell carcinoma) and a secondary skin metastasis from neuroendocrine carcinomas of different sites.[3-5]
The primary cutaneous carcinoid tumor is a very rare disease. The cell of origin for a primary cutaneous carcinoid tumor may be epidermal Merkel cells or epithelial stem cells with neuroendocrine differentiation.[3-5] Often it appears as solitary nodules with long-standing (≤ 10 ≥ years) and gradual growth. However, in this case, the patient's history, associated with the clinical aspects, determined a good discrimination in the diagnosis.
Merkel cell carcinoma was taken into account in the differential diagnosis, because our tumor was of neuroendocrine origin in the skin. The clinical location and presentation of our tumor were compatible with a Merkel cell carcinoma, but not the age of the patient; indeed, the average age of people with Merkel cell carcinoma is usually 67–69 years and only 5% of cases occur before the age of 50 years. In addition to neuroendocrine markers, the cells typically show a dot-like staining pattern for CK20.[3-5]
Our tumor showed typical epithelioid cells with trabecular pattern and was negative for CK20; so, the age of the patient associated with the clinical history and with the histopathological and immunohistochemical aspects of the lesion, ruled out a possible diagnosis of Merkel cell carcinoma.
We reported a case of a 43-year-old woman with a metastasis of a carcinoid tumor of the lung because we consider it appropriate that dermatopathologists recognize this diagnosis in order to avoid misdiagnosis and to refer the patient for therapeutic procedures.