Abstract
Purpose
Immunosuppressed solid organ transplant recipients (SOTRs) have an increased risk of developing cutaneous squamous cell carcinomas (cSCCs) with metastatic potential. This study sought to determine the rate of regional lymph node involvement in a large cohort of solid organ transplant patients with cutaneous head and neck squamous cell carcinoma.
Materials and methods
A retrospective chart review was performed on solid organ transplant patients with head and neck cutaneous squamous cell carcinoma treated at a tertiary academic medical center from 2005 to 2015.
Results
130 solid organ transplant patients underwent resection of 383 head and neck cutaneous squamous cell carcinomas. The average age of the patient was 63. Seven patients (5%) developed regional lymph node metastases (3 parotid, 4 cervical lymph nodes). The mean time from primary tumor resection to diagnosis of regional lymphatic disease was 6.7 months. Six of these patients underwent definitive surgical resection followed by adjuvant radiation; one patient underwent definitive chemoradiation. 6 of the 7 patients died of disease progression with a mean survival of 15 months. The average follow up time was 3 years (minimum 6 months).
Conclusions
Solid organ transplant recipients with cutaneous squamous cell carcinoma of the head and neck develop regional lymph node metastasis at a rate of 5%. Regional lymph node metastasis in this population has a poor prognosis and requires aggressive management and surveillance.
1
Introduction
Solid organ transplant recipients (SOTRs) have an increased risk for cutaneous squamous cell carcinoma (cSCC). For example, renal transplant recipients have up to an 82-fold increase increased risk of invasive cSCC compared to non-transplanted patients . The risk of developing cSCC correlates with the degree and length of immunosuppression . Compared to immunocompetent hosts, SOTRs develop cSCCs with higher rates of regional recurrence and a worse prognosis if metastases develop .
The overall rate of metastasis for cSCC is 2–5% . Immunosuppression is an independent risk factor for regional lymph node involvement . Other risk factors for metastasis include the maximum clinical diameter (> 2 cm) and thickness of the primary tumor, poor differentiation, and location on the lip, ear, or posterior auricular area. In a large study of 615 patients, only tumors > 2 mm in thickness were found to metastasize . The rate of regional lymph node metastasis for immunocompromised patients has been previously reported as high as 12% .
Despite the increased risk and poor prognosis for of regional lymph node metastasis in SOTRs, there is a lack of consensus for strategies to manage clinically node negative patients. To determine the rate of regional lymph node metastases and the course of metastatic disease, we performed a retrospective chart review of all solid organ transplant patients with head and neck cutaneous SCC treated at our institution from 2005 to 2015.
2
Material and methods
This study was approved by the University of Pennsylvania Institutional Review Board. A retrospective chart review was performed for all SOTRs who underwent surgery between 2005 and 2015 for a cSCC of the head and neck at the Hospital of the University of Pennsylvania Department of Dermatology and/or Otorhinolaryngology. Patients were identified by searching the Penn Dermatology Oncology Center’s operative database for SOTRs who had undergone Mohs surgery for cSCCs on the head and neck. A minimum of 6 months of follow up was required, which excluded 15 patients with 34 cancers. The charts of all patients who met inclusion criteria were then reviewed for evidence of regional failure and subsequent treatment. Patient demographics, tumor characteristics, surgical details, and immunosuppressive regimens were recorded. Statistical analysis was performed using SAS 9.3 (SAS Institute Inc., Cary, North Carolina).
2
Material and methods
This study was approved by the University of Pennsylvania Institutional Review Board. A retrospective chart review was performed for all SOTRs who underwent surgery between 2005 and 2015 for a cSCC of the head and neck at the Hospital of the University of Pennsylvania Department of Dermatology and/or Otorhinolaryngology. Patients were identified by searching the Penn Dermatology Oncology Center’s operative database for SOTRs who had undergone Mohs surgery for cSCCs on the head and neck. A minimum of 6 months of follow up was required, which excluded 15 patients with 34 cancers. The charts of all patients who met inclusion criteria were then reviewed for evidence of regional failure and subsequent treatment. Patient demographics, tumor characteristics, surgical details, and immunosuppressive regimens were recorded. Statistical analysis was performed using SAS 9.3 (SAS Institute Inc., Cary, North Carolina).
3
Results
130 solid organ transplant patients underwent Mohs resection of 383 head and neck cutaneous SCCs. The average age at the time of resection was 62 years (standard deviation ± 11). Patients underwent surgery for an average of 3.5 (range 1–13) additional head and neck cSCC during the mean follow up period of 3.36 years. The transplant type, immunosuppressive regimen, and primary lesion locations are shown in Tables 1 and 2 .
| Transplant type | All patients | Regional failures | |
|---|---|---|---|
| N | % | N | |
| Heart | 16 | 12% | 2 |
| Kidney | 47 | 36% | 3 |
| Liver | 18 | 14% | 2 |
| Lung | 35 | 27% | |
| Liver/kidney | 10 | 8% | |
| Heart/kidney | 2 | 2% | |
| Kidney/pancreas | 1 | 1% | |
| Heart/lung | 1 | 1% | |
| Immunosuppressive regimen | |||
| Tacrolimus, prednisone | 29 | 22% | 4 |
| Tacrolimus, prednisone, mycophenolate mofetil | 24 | 18% | 2 |
| Tacrolimus | 19 | 15% | 1 |
| Azathioprine, tacrolimus, prednisone | 12 | 9% | |
| Other single agent | 4 | 3% | |
| Other double agent | 24 | 18% | |
| Other triple agent | 14 | 11% | |
| Other | 4 | 3% | |
| Location of primary cSCC | |||
| Scalp | 60 | 16% | 4 |
| Forehead, brow | 81 | 21% | |
| Periorbital | 11 | 3% | |
| Ear, mastoid | 54 | 14% | 2 |
| Preauricular, periparotid | 52 | 14% | 1 |
| Nasal | 18 | 5% | |
| Cheek | 41 | 11% | |
| Labial | 22 | 6% | |
| Cervical | 42 | 11% | |
| Chin | 2 | 1% | |
| All patients | Regional failures | ||
|---|---|---|---|
| Anatomic depth of tumor invasion | |||
| Epidermis | 12 | 3% | |
| Dermis | 327 | 85% | 1 |
| Subcutaneous Fat | 28 | 7% | 3 |
| Muscle | 7 | 2% | |
| Cartilage | 3 | 1% | 1 |
| Other | 6 | 2% | 2 |
| T stage (AJCC) | |||
| T1 | 281 | 73% | |
| T2 | 102 | 27% | 7 |
| T3 | 0 | 0% | |
| T4 | 0 | 0% | |
| T stage (Brigham and women’s) | |||
| T | 265 | 69% | |
| T2a | 91 | 24% | 1 |
| T2b | 26 | 7% | 6 |
| T3 | 1 | 0% | |
| T4 | 0 | 0% | |
Seven patients developed regional lymph node failure (4 cervical lymph nodes, 3 parotid). These patients’ metastatic disease was detected on clinical exam by the physician or the patient themselves. Six of these patients underwent definitive surgical resection of their regional disease followed by adjuvant radiation (±) chemotherapy. One patient underwent primary chemoradiation due to medical comorbidities that prohibited surgery. The mean time from the resection of the primary lesion to presentation with regional lymph node involvement was 6 months (SD ± 4). Six of the seven patients died from locoregional disease progression or distant metastases. The mean time of regional lymph node treatment to death was 15 months (SD ± 6). These patients are discussed in Table 3 .
