What is the treatment approach for skin lesions associated with neuroendocrine tumors?

Treatment Approach for Skin Lesions Associated with Neuroendocrine Tumors

For skin lesions associated with neuroendocrine tumors, treatment should follow the NCCN Guidelines for Neuroendocrine Tumors, with specific consideration for the primary tumor site, differentiation, and extent of disease. 1

Diagnostic Evaluation

• Skin lesions may represent either primary neuroendocrine tumors of the skin (Merkel cell carcinoma) or cutaneous metastases from non-cutaneous neuroendocrine primaries 2, 3
• Comprehensive diagnostic workup should include:
  • Histopathologic examination with immunohistochemical staining for neuroendocrine markers (synaptophysin, chromogranin A, neuron-specific enolase) 4, 5
  • Determination of tumor differentiation and Ki-67 proliferation index 5
  • Baseline biochemical tests including chromogranin A and 5-HIAA 1, 5
  • Multiphase contrast-enhanced CT or MRI to identify primary tumor and assess for metastatic disease 1, 6
  • Somatostatin receptor scintigraphy (Octreoscan) or 68Ga-DOTA-octreotate PET for tumor localization 1, 4, 5

Treatment Approach

For Primary Cutaneous Neuroendocrine Tumors

• Complete surgical excision with negative margins is the primary treatment for localized disease 2
• Regional lymph node dissection should be considered due to high risk of lymph node metastases 2
• For metastatic disease, treatment follows the same principles as for metastatic neuroendocrine tumors from other sites 1

For Cutaneous Metastases from Non-Cutaneous Neuroendocrine Tumors

• Treatment should be directed at the underlying primary tumor 3
• Surgical resection of isolated cutaneous metastases may be considered for symptom control 1
• For widespread cutaneous metastases, systemic therapy options include:

Systemic Therapy Options

• Somatostatin analogs (octreotide, lanreotide) for symptom control in patients with somatostatin receptor-positive tumors 1
• Cytotoxic chemotherapy regimens based on tumor differentiation:
  • For well-differentiated tumors: 5-FU, dacarbazine and epirubicin; or streptozocin combinations with 5-FU and/or doxorubicin 1
  • For poorly differentiated tumors: platinum-based chemotherapy (cisplatin or carboplatin) with etoposide 1, 7
• Targeted therapies such as everolimus may be considered in appropriate cases 7
• Tumor-targeted radioactive treatment for patients with high uptake on somatostatin receptor scintigraphy 1

Local Therapies

• External beam radiotherapy may provide relief for symptomatic cutaneous lesions 1, 7
• Ablative therapies may be considered for limited metastatic disease 1, 7

Follow-up Recommendations

• Patients should be followed at 3-month intervals during treatment with cytotoxic agents or biological therapy 1
• Imaging evaluation should be performed at least every 6 months for metastatic disease 1
• Biochemical markers such as chromogranin A should be monitored every 3-6 months 1

Common Pitfalls and Caveats

• Cutaneous metastases from non-cutaneous neuroendocrine tumors must be distinguished from primary Merkel cell carcinoma as management differs 3
• Immunohistochemical stains (CK20, CK7, TTF-1) may help identify the primary site but results can vary and are often non-specific 3
• Complete radiologic imaging and clinical correlation are essential for identifying the primary neoplasm 3
• Neuroendocrine tumors can metastasize to multiple sites including skin, and a comprehensive evaluation for other metastatic sites is necessary 1, 8