Merkel cell carcinoma of the head and neck: effect of surgical excision and radiation on recurrence and survival

BACKGROUND: Merkel cell carcinoma is a rare malignant neoplasm of the skin that most often arises in the head and neck region. Despite the innocuous appearance of the primary lesion, Merkel cell carcinoma often has an aggressive clinical course with frequent locoregional recurrences and distant metastases. We evaluated the association of the width of surgical margins and the use of postoperative radiation therapy with locoregional control and survival rates. METHODS: The medical records of 66 patients with head and neck Merkel cell carcinoma seen between 1945 and 1995 were retrospectively reviewed. The Fisher exact test was used to compare outcomes. Kaplan-Meier survival curves were constructed. RESULTS: Eighteen patients for whom there was adequate information were divided into the following groups according to the width of their surgical margins: smaller than 1 cm, 1 to 2 cm, and larger than 2 cm. No statistical difference in locoregional control or survival was found among these groups owing to the small patient population. In contrast, a comparison of the patients who did (n = 26) and did not (n = 34) receive postoperative radiation therapy revealed a significant difference in local (3 [12%] vs 15 [44%], respectively; P<.01) and regional (7 [27%] vs 29 [85%], respectively; P<.01) recurrence rates. There was, however, no significant difference in the disease-specific survival between these groups (P = .30). Distant disease developed in 36% of all patients regardless of therapy. CONCLUSIONS: Any effect of the width of surgical margins on outcome was not detectable in the small number of patients analyzed. The use of postoperative radiation therapy was associated with a significant improvement in locoregional control. There was no detectable influence of the type of initial therapy on the rates of distant metastases or on survival. Future therapeutic innovations should be directed toward controlling the development of distant metastases in patients with Merkel cell carcinoma.     

Merkel cell-carcinoma in the parotid gland--review of literature and case report

Merkel cell carcinoma is a rare malignant primary tumor of the skin, which develop typically in the elderly in the sun exposed areas of the skin, most commonly in the head and neck region. This tumor is very aggressive with a high rate of regional and distant metastases, marked propensity for local et regional recurrence, and very poor survival. Skin lesions are typically red or purple and present as a solitary dome-shaped nodule or indurated plaque. The recognition of such tumor in not difficult, but in same cases, when the tumor infiltrate deeper organs and structures it may cause some problems. We describe a case of 86 years old women who was operated in our department with an initial diagnosis of parotid tumor infiltrating the skin of the preauricular region and the facial nerve. The histopatological and immunohistochemical examination of the tumor showed that it was Merkel cell carcinoma, which in fact developed in the skin and infiltrated parotid gland and facial nerve. After operation patient received 2 courses of palliative radiation. Until now during a 4,5 years follow up there was no recurrence of the tumor and the patient is well.     

Merkel cell carcinoma of the skin with leptomeningeal metastases

Merkel cell carcinoma is a rare skin tumor that is thought to arise from epithelial cells that have undergone neuroendocrine differentiation. It usually presents in older adults and has a slight male predominance. The most frequent site of occurrence is in the head and neck. It is an aggressive disease that has a high rate of local-regional and distant recurrence. Optimal treatment is controversial but generally consists of surgery and adjuvant radiotherapy. The role of chemotherapy is less defined. This report documents the first known case of Merkel cell carcinoma with perineural spread to the central nervous system with leptomeningeal dissemination. Whether this represents a more aggressive variant is unknown. Regardless, this pattern of spread is likely a rare event.     

Skin and Eye: Uncommon Sites of Distant Metastasis from Tongue Base Squamous Cell Carcinoma

The frequency of non-lymphatic distant metastases from primary head and neck squamous cell carcinoma (SCC) appears to be higher than previously presumed. The general conditions of the affected patients, who usually also present with locoregional recurrences, are so impaired as to limit the use of available methods for diagnosing the distant spread of head and neck SCC. The incidence reported in autopsy studies is approximately three to four times higher than that in clinical studies. Lung metastases from head and neck SCC are most common, followed by metastases to bone and liver. Metastases to the skin are unusual. Secondary ocular localizations of head and neck SCC are exceedingly rare. We report the first case of synchronous intraocular (involving the choroid and vitreous body) and cutaneous metastases from a recurrent tongue base SCC in a 64-year-old woman who had undergone radiotherapy, bilateral neck dissection and chemotherapy. Cytological evaluation of vitreous aspirate and histological diagnosis of the skin lesion were performed < 1 month before the patient's death. Skin metastases occur in 1–4% of patients with diagnosed head and neck SCC and are usually associated with advanced or recurrent disease. To the best of our knowledge, fewer than 10 cases of ocular metastases from head and neck SCC have been reported. The average survival time after diagnosis of ocular or skin metastases from head and neck SCC is ≈ 7 months. Treatment for eye and skin metastases is palliative and rarely alters patient outcome.     

Skin and eye: uncommon sites of distant metastasis from tongue base squamous cell carcinoma

The frequency of non-lymphatic distant metastases from primary head and neck squamous cell carcinoma (SCC) appears to be higher than previously presumed. The general conditions of the affected patients, who usually also present with locoregional recurrences, are so impaired as to limit the use of available methods for diagnosing the distant spread of head and neck SCC. The incidence reported in autopsy studies is approximately three to four times higher than that in clinical studies. Lung metastases from head and neck SCC are most common, followed by metastases to bone and liver. Metastases to the skin are unusual. Secondary ocular localizations of head and neck SCC are exceedingly rare. We report the first case of synchronous intraocular (involving the choroid and vitreous body) and cutaneous metastases from a recurrent tongue base SCC in a 64-year-old woman who had undergone radiotherapy, bilateral neck dissection and chemotherapy. Cytological evaluation of vitreous aspirate and histological diagnosis of the skin lesion were performed < 1 month before the patient's death. Skin metastases occur in 1-4% of patients with diagnosed head and neck SCC and are usually associated with advanced or recurrent disease. To the best of our knowledge, fewer than 10 cases of ocular metastases from head and neck SCC have been reported. The average survival time after diagnosis of ocular or skin metastases from head and neck SCC is 7 months. Treatment for eye and skin metastases is palliative and rarely alters patient outcome.     

Merkel cell carcinoma (endocrine carcinoma of the skin) of the head and neck

Merkel cell carcinoma, also known as endocrine carcinoma of the skin, is a recently recognized and particularly aggressive form of skin cancer that exhibits histologic features similar to those of endocrine malignant neoplasms arising from other tissues. Forty-one patients with Merkel cell carcinoma arising from the cutaneous surfaces of the head and neck were seen at the University of Texas M. D. Anderson Hospital, Houston, between 1966 and 1983. Regional lymph node metastasis occur early and frequently, with a 79% overall incidence observed during the course of the disease. Treatment should consist of a wide resection of the primary tumor. A regional lymphadenectomy, when feasible, is successful in controlling nodal metastases. Postoperative radiation is recommended as an important adjuvant.     

The interesting case -- case no. 68. Metastasis of a small-cell bronchial carcinoma to the parotid gland

We present a case of a metastasis to the parotid gland from a small cell carcinoma of lung. The patient noted swelling in right parotid region without pain and saw an otorhinolaryngologist. There was no facial nerve palsy. He was admitted to our hospital. The total parotidectomy with facial nerve preserving was performed. The pathological findings indicated small cell carcinoma. After receipt of this report, we examined the lungs. An abnormal shadow could be found in the chest X-rays. CT revealed a lung tumor on a left site which was determined to be small cell carcinoma by transbronchial lung biopsy. Metastasis to the parotid glands from any distant primary site is quite unusual. In most cases of secundary parotid involvement of malignant tumors primary tumors originated from the head and neck region. Primary tumors in the neighborhood are the skin of the head and neck and the mucosa of the upper airway and digestive tract. Distant metastases to the parotid gland have been reported to arise from bronchial carcinoma, renal carcinoma, colonic carcinoma, prostat and breast. The distinction between primary salivary glands tumors and metastases of other primary tumors is difficult often. Histologic and immunhistological methods can be helpful.     

Bilateral synchronous tonsillar carcinoma: a case series and review of the literature

We present the first dedicated case series of bilateral synchronous tonsillar carcinoma and discuss the role of bilateral tonsillectomy as a diagnostic tool. The occurrence of multiple head and neck tumours is well recognised; however, reports of bilateral synchronous tonsillar carcinoma are rare. A literature review reveals only 12 cases of bilateral synchronous tonsillar carcinoma described in the international literature in the past 15 years. We present a further three cases confirmed following bilateral tonsillectomy. In conclusion, bilateral tonsillectomy has in many centres been established as a standard diagnostic and therapeutic procedure for patients who have cervical metastases from a head and neck cancer of unknown primary site. It is likely the true incidence of bilateral synchronous tonsillar carcinoma is underestimated and under-reported. We recommend bilateral tonsillectomy for patients with suspected or proven unilateral tonsillar carcinoma as well as those with cervical metastases from unknown primary site.     

Noncervical lymph node metastasis from head and neck cancer.

Nonregional lymph node dissemination must be classified as distant metastasis but axillary and mediastinal metastases can be part of a regional dissemination of the disease. Metastases to lymph nodes of the upper mediastinum are very common among patients with subglottic, hypopharynx and thyroid carcinomas. Axillary metastases are found at autopsy in 2-9% of the patients who died of head and neck squamous cell carcinoma (SCC) and are frequently associated with skin implantation in aggressive recurrent head and neck carcinomas. The possible explanations for this location of metastasis were retrograde dissemination due to lymph system blockage, further tumor dissemination after a parastomal recurrence, hematogenous dissemination, and metastasis from a second primary tumor. Patients with distant metastasis have been considered incurable and only palliative treatment was instituted. Treatment planning for cases with axillary metastasis must take in consideration the likelihood of other regional recurrences and/or distant metastasis. Also, the presence of a second primary tumor must be ruled out. Whenever axilla is the only site of cancer recurrence, a standard axillary dissection must be considered. Upper mediastinal metastases from subglottic and hypopharyngeal cancer are managed by paratracheal and mediastinal dissection through the neck and postoperative radiotherapy.     

Oropharyngeal metastasis of a Merkel cell carcinoma of the skin

Merkel cell carcinoma (MCC) is an aggressive neuroendocrine tumor of the skin characterized by frequent local and regional recurrence, a high incidence of distant metastases and therefore a high mortality. Here, we report a case of an oropharyngeal metastasis of a Merkel cell carcinoma of the skin localized at the left base of the tongue causing dysphagia and the sensation of globus pharyngeus. The unusual metastatic site is presented, and diagnosis and treatment are discussed.     

Significance of distant metastases and secondary cancers as a cause of death in patients with ENT cancers

Hospital charts and autopsy reports of 148 patients with head and neck carcinoma were reviewed in order to assess the mortality from distant metastases and other primaries. 49% of the patients with uncontrolled local or regional disease died with distant metastases. Only 4% of these patients had a second primary. In patients with controlled local and regional disease the opposite was found. Distant metastases were uncommon (9%). Yet, 44% of the patients died of a second primary located in the upper aerodigestive tract or lungs. If life expectancy in patients with controlled head and neck carcinoma is to be improved, early detection of second primaries is important. As only 9% of patients with locally controlled disease die from distant metastases adjuvant chemotherapy is not indicated.     

Merkel cell carcinoma of the auricle

Merkel cell carcinoma is a rare, although increasingly recognized, malignant tumor of the skin. The most common site of occurrence is the head and neck (50%). Only five cases of this tumor on the auricle have been reported previously. We present a further such case. The incidence, clinical features, diagnosis, prognosis, and treatment of the Merkel cell carcinoma are discussed. Received: 21 August 2000 / Accepted: 18 September 2000     

Merkel cell carcinoma of the head and neck

Merkel cell carcinoma is a rare cutaneous tumour that typically arises in the head and neck area of elderly patients. The tumour often follows an aggressive course with frequent local recurrences and (regional) metastases, especially when localized above the clavicles. Five patients with a Merkel cell carcinoma of the head and neck, treated in our institute since 1984, are presented, illustrating the need for radical initial treatment consisting of surgery and radiotherapy, and showing how rapidly progressive the disease can be. Four of the five patients were cured of disease by a combination of surgery and radiotherapy.     

Incidence and sites of distant metastases from head and neck cancer.

The incidence of distant metastases in head and neck squamous cell carcinoma (SCC) is relatively small in comparison to other malignancies. Distant metastases adversely impact survival and may significantly affect treatment planning. The incidence of distant metastases is influenced by location of the primary tumor, initial T and N stage of the neoplasm, and the presence or absence of regional control above the clavicle. Patients with advanced nodal disease have a high incidence of distant metastases, particularly in the presence of jugular vein invasion or extensive soft tissue disease in the neck. Primary tumors of advanced T stages in the hypopharynx, oropharynx and oral cavity are associated with the highest incidence of distant metastases. Pulmonary metastases are the most frequent in SCC, accounting for 66% of distant metastases. It may be difficult to distinguish pulmonary metastasis from a new primary tumor, particularly if solitary. Other metastatic sites include bone (22%), liver (10%), skin, mediastinum and bone marrow. An important question remains as to how intensely pre- and postoperative screening for distant metastases should be performed. Preoperative chest X-ray is warranted in all cases. If the primary tumor and nodal status place the patient at high risk for pulmonary metastasis, then preoperative computed tomography scan of the chest should be done. Screening for distant metastases at other sites is usually not indicated in SCC of the upper aerodigestive tract. Postoperatively, annual X-rays of the chest are usually sufficient, but in high-risk situations a chest X-ray performed every 3-6 months may be beneficial. Certain histologic types of primary tumor have greater or lesser propensity to metastasize distantly, and have a different natural history. Adenoid cystic carcinoma metastasizes frequently, even in the absence of extensive local or regional disease. Basaloid squamous cell carcinoma and neuroendocrine carcinomas also metastasize widely. Extensive evaluation for distant metastases is justified for these tumors. Knowledge of the natural history of various neoplasms and the factors that contribute to distant metastases as well as good judgement are essential for cost-effective treatment planning and decision-making with regard to pre- and postoperative evaluation for distant metastases in cancer of the head and neck.     

Metastatic Cutaneous Squamous Cell Carcinoma of the Head and Neck Region

Cutaneous squamous cell carcinoma has a relatively low metastatic rate (0.5% to 16%), but patients with the disease should always be evaluated for possible regional nodal involvement. We reviewed the records of 37 patients with metastatic disease among the 388 patients with head and neck cutaneous squamous cell carcinoma who were treated at New York University Medical Center between 1961 and 1992. In this group of patients the most common primary site was the cheek or preauricular region and the most common metastatic site was the level I neck lymph nodes. Seven patients (18%) had metastases at initial presentation. Among the remaining patients the average time to the development of metastases was 19 months. Nineteen patients (51%) had recurrence at the primary site before metastasis; 11 (30%) developed metastases with control of the primary tumor. Analysis of the records of 31 patients treated for cure revealed that 13 were treated by surgery, 2 by radiation therapy, and 16 by a combination of surgery and radiation therapy. During the mean follow-up period of 49 months, 11 (35%) of these 31 patients died of their disease. Recurrence of the primary tumor appeared to increase the risk for nodal and distant metastases.     

Screening for Distant Metastases in Patients With Head and Neck Cancer: Is Chest Computed Tomography Sufficient?

OBJECTIVES/HYPOTHESIS: The detection of distant metastases during screening influences the choice of treatment in patients with head and neck squamous cell carcinoma. A previous study in the authors' institution showed that chest computed tomography (CT) scan was the most important screening technique. Different clinical risk factors in patients with head and neck squamous cell carcinoma for the development of distant metastases were identified. STUDY DESIGN: Retrospective cohort study. METHODS: To evaluate the authors' diagnostic strategy, the accuracy of screening for distant metastases with chest CT in 109 consecutive patients with head and neck squamous cell carcinoma with risk factors between 1997 and 2000 was retrospectively analyzed. RESULTS: Preoperative screening with CT revealed 20 patients (18%) with lung metastases and 1 liver metastasis. Despite negative screening with chest CT, 9 (11%) patients developed distant metastases within 12 months during follow-up. Sensitivity of the chest CT was 73%; the specificity was 80%. CONCLUSION: Although chest CT frequently detects distant metastases, there seems to be a need for a more sensitive and whole-body screening technique.     

Detection of Epstein-Barr virus in metastatic lymph nodes of patients with nasopharyngeal carcinoma and a primary unknown carcinoma

BACKGROUND: Nasopharyngeal carcinoma is often associated with neck lymph node (LN) metastases, which in many cases is the only manifestation of this disease. The submucosal and infiltrative characteristics of nasopharyngeal carcinoma make this type of cancer difficult to diagnose. Nasopharyngeal carcinoma has also been reported to be strongly associated with the Epstein-Barr virus. METHODS: We examined 36 nasopharyngeal carcinomas (from 30 primary sites and from 6 metastasized LNs), 13 metastasized LNs of other head and neck cancers, and 12 primary unknown neck metastases using an in situ hybridization technique. RESULTS: In the nasopharyngeal carcinomas, in situ hybridization with an Epstein-Barr virus-encoded small RNA identified the Epstein-Barr virus in 20 (67%) of the 30 primary sites and in 3 (50%) of the 6 metastasized LNs. Epstein-Barr virus was not detected in metastasized LNs of other head and neck cancers, but was detected in 1 of the primary unknown neck metastases. CONCLUSION: In situ hybridization using a digoxigenin-labeled Epstein-Barr virus-encoded small RNA probe is useful for the differential diagnosis of metastasized LNs when the primary site is unknown.     

Screening for distant metastases in patients with head and neck cancer: what is the current clinical practice?

Objectives: The detection of distant metastases during screening influences the choice of treatment in patients with head and neck squamous cell carcinoma (HNSCC). There is no consensus on the diagnostic technique that has to be used nor on the subgroup of HNSCC patients that may benefit from screening. Design: Questionnaire on current practice concerning the diagnostic work‐up in HNSCC patients for screening for distant metastases. Participants: Investigators in the 12 otolaryngology / head and neck and seven oromaxillofacial departments treating head and neck cancer in the Netherlands. Results: The response rate was 100%. Indications for screening were cervical lymph node metastases (63%), mutilating surgery (58%), locoregional recurrence (47%), advanced T‐stage (32%), second primary tumour (21%). Diagnostic techniques routinely used for screening besides chest X‐ray were chest CT (84%), liver ultrasound (53%), liver CT (16%) and bone scintigraphy (42%). Forty‐two per cent of the clinicians were not satisfied with the current methods of screening. Conclusion: This survey shows a substantial variation in indications and diagnostic techniques used for screening for distant metastases between the major institutions treating head and neck cancer in the Netherlands. There is a need for guidelines for screening for distant metastases in patients with head and neck cancer.     

Merkel cell carcinoma

PURPOSE: To determine the natural history and treatment outcomes for patients with Merkel cell carcinoma. METHODS: Review of the literature. RESULTS: The probability of regional node involvement at presentation exceeds 50%; few patients present with distant metastases. Comprehensive treatment of the primary site and regional lymphatics with surgery or radiotherapy results in the highest likelihood of cure. The role of adjuvant chemotherapy remains investigational. CONCLUSION: The probability of regional dissemination at diagnosis is high. The optimal treatment is resection of the primary tumor and treatment of the regional lymphatics. Resection of all gross tumor should be accomplished followed by local-regional radiotherapy in most patients.     

Recurrence rates after selective neck dissection in the N0 irradiated neck

OBJECTIVES: To define patterns of subclinical metastases in irradiated N0 necks with recurrent or persistent primary site disease and to determine the regional control rate when selective neck dissection (SND) is used in this setting. PATIENTS AND INTERVENTION: Individuals included were previously treated for head and neck squamous cell carcinoma with primary radiation therapy or chemoradiotherapy. All had recurrent or persistent disease at the primary site, with no clinical or radiographic evidence of nodal disease. The patients underwent surgical treatment of the primary site along with site-specific SND and were required to undergo at least 1 year of follow-up. Subsequent recurrence at the primary site disqualified the patient from further evaluation. MAIN OUTCOME MEASURE: Regional tumor control. RESULTS: Forty-three patients meeting the inclusion criteria underwent 59 SNDs (levels dissected: I-IV [n = 22], II-IV [n = 34], and I-III [n = 3]). Sixteen specimens were positive for nodal disease. The charts of 26 patients, who underwent a total of 35 SNDs, were available for review after 1 year (none of the patients involved died of disease in the neck). There were no neck recurrences (mean follow-up, 25 months; median, 21 months). All patients with more than 2 occult nodal metastases experienced primary site recurrence or distant metastases. CONCLUSIONS: In this small cohort, SND in previously irradiated patients with recurrent primary disease but clinically negative necks has resulted in excellent tumor control in the neck. The usual patterns of nodal spread do not appear to be significantly altered with primary site recurrence after radiation therapy. The presence of more than 2 positive nodes in the neck specimen correlates with poor prognosis.