Merkel cell carcinoma of the head and neck: report of seven cases

Merkel cell carcinoma is a rare and aggressive primary cutaneous neoplasm. Clinically it is characterized by innocuous appearance, as a fast growing asymptomatic nodule or plaque. Head and neck are the most common sites of presentation (50%). The treatment is based on local surgery completed with cervical lymph node dissection, radiotherapy, chemotherapy and other treatments depending on the staging. Sentinel lymph biopsy seems to be useful for its treatment. Tumour staging is the only prognostic factor related to overall survival. Prognosis is very poor due to the high incidence of loco-regional recurrence and metastases. Seven cases of Merkel cell carcinoma of the head and neck are reported. These were treated in our Department over the last two and a half years. A literature review was made.     

Merkel cell carcinoma: our experience in this rare pathology

Merkel cell carcinoma (MCC) was first described in 1972 by Toker, who described five cases of the so-called "trabecular carcinoma of the skin ". MCC is a rare, aggressive skin cancer that affects mainly the elderly. Sun exposed areas are mainly affected, specially the head and neck. Immunohistochemical analysis is essential to reach a correct diagnosis. According to the origin of MCC, the tumor expresses both epithelial and neuroendocrine markers. MCC has a propensity for recurrence, regional and distant metastases. Several treatment options are available, such as surgical excision or Moh's surgery, accompanied by neck dissection or radio and chemotherapy in advanced cases. The present study aims to evaluate the clinical behaviour and the evolution of five cases of this disease that were treated at our institution (reference to 1100000 inhabitants) in the last five years. It is stressed on the bad prognosis of this pathology, which presents high rates of locoregional recurrence, even though the recent advances in radio and chemotherapy.     

Merkel cell carcinoma of the alveolar mucosa in a young adult: A rare case report

Merkel cell carcinoma (MCC) is an extremely rare and aggressive primary neuroendocrine neoplasm of the skin with a poor prognosis. It occurs mainly in the sixth and seventh decades of life and is usually associated with damage caused by over exposure to the sun. Its occurrence in intraoral mucosal sites is rare, and we know of only six reported cases. We report a rare case of MCC that arose in the alveolar mucosa of a young adult.     

Management of regional metastatic disease in cutaneous malignancy of the head and neck. 3. Merkel cell carcinoma

This is the third of three articles that give an overview of the current evidence for management of the neck and parotid in patients with cutaneous cancers of the head and neck. In this paper we discuss Merkel cell carcinoma (MCC) and review the latest evidence for management of the regional nodes.     

Management of early stage cutaneous Merkel cell carcinoma of the head and neck

Merkel cell carcinoma (MCC) is a rare but aggressive skin cancer of neuroendocrine origin. As a result, few large studies have been published, and we know of even fewer on disease of the head and neck alone. The most appropriate way to manage patients with early local disease and no sign of metastases neck is controversial. We reviewed management of early cutaneous MCC of the head and neck in 8 hospitals in the United Kingdom over 12 years between 1999 and 2011 (the largest head and neck series in Europe to date), and identified 39 patients (19 men and 20 women) with early disease according to a well recognised classification. A total of 24 patients had stage Ia disease, 11 had stage Ib disease, and 4 were unclassified. Five of those with stage Ia disease developed regional metastases and 7 with stage Ib disease developed regional recurrence. The 2-year overall survival for stage Ia and Ib disease was 62% and 27%, respectively. Our study shows that prognosis is poor after conservative surgical management of stage I disease. Management of the neck is still controversial, and a meta-analysis of all the published data is needed to establish best practice statistically.     

Merkel cell carcinoma of the head and neck in the south-east of England

Merkel cell carcinoma (MCC) is a rare and highly aggressive neuroendocrine malignancy of the skin. Its incidence is increasing with half of cases involving the head and neck. To the best of our knowledge, few large studies have been published in the UK, and to date this is the largest reported series of head and neck MCC. We retrospectively reviewed the outcomes of patients with MCC in three hospitals in the south-east of England over a 12-year period (2008–2019). Diagnosis was based on histological data following biopsy. Overall survival and disease-specific survival were calculated using Kaplan–Meier and log-rank tests. Fifty-eight patients met the inclusion criteria (24 stage I, 22 stage II, 9 stage III, and 3 unclassified). Median disease-free survival was 36 months (95% CI 0 to 77.2) and median overall survival 50 months (95% CI 29.9 to 70). Overall five-year survival was 34.4% (95% CI 17% to 52%) with two-year survival at 62% (95% CI 48% to 76%). Five-year disease-free survival was 26.7% (95% CI 17 to 52%) with two-year disease-free survival at 54% (95% CI 40% to 68%). To date, this is the largest UK based study reporting overall and disease-free survival associated with MCC of the head and neck. Half the patients presented late, and surgery was the mainstay of treatment, augmented by adjuvant radiotherapy. There is a need to better stratify patients at risk of developing metastatic disease, with the use of sentinel lymph node biopsy and positron-emission tomography-computed tomography (PET-CT), as immunotherapy and targeted agents are now available to treat advanced disease.     

A SEER analysis of survival and prognostic factors in merkel cell carcinoma of the head and neck region

While Merkel cell carcinoma (MCC) of the head and neck is highly malignant, it remains poorly characterized due to its rarity. The purpose of this study was to examine prognostic factors for overall survival (OS) and disease-specific survival (DSS) in patients with MCC of the head and neck region. The Surveillance, Epidemiology and End Results registry was reviewed for patients diagnosed between 1984 and 2016 with histologically confirmed, primary MCC of the head and neck region. A total of 2818 patients met the inclusion criteria, with a median age at diagnosis of 77 years. At five and 10 years, respectively, the OS was 42.4% and 25.1% and the DSS was 67.9% and 64.1%. Multivariate Cox analysis indicated that predictors of decreased DSS included age at diagnosis ≥75 years, white race, increasing tumor spread, lymph node involvement and either the lip or the scalp/neck as a primary site. When adjusting for the aforementioned factors, tumor depth was not found to be a prognostic factor for DSS. We anticipate these results will help clinicians to counsel patients regarding expectations and potential prognosis.     

Second primary head and neck squamous cell cancers with aggressive behavior in patients with chronic myeloid leukaemia

Patients with chronic myeloid leukaemia (CML) are at considerable risk of developing second primary neoplasms. However, mucosal squamous cell cancers (SCCs) of the head and neck have not been reported. We review the data of 7 patients with mucosal SCC of the head and neck that presented as metachronous second primary tumours in patients with CML. All 7 patients were men (median age 48 years, range 31-67) (site:oral cavity n=6, hypopharynx n=1). The median interval between diagnosis of CML and head neck cancer was 6 years (range 2-15). Treatment was curative in 4 and palliative in 3. At median follow up of 14 months (range 2-44), 3 patients had died of head and neck cancer, 1 of CML, and 3 were alive and free of disease. Mucosal cancers of the head and neck can occur in long-term survivors of CML. They are aggressive and tend to recur.     

The importance of the head and neck region in regression of advanced MCC: a clinical report

This paper presents the case of a 76-year-old woman who experienced a total regression of a Merkel cell carcinoma (MCC). The primary site of the tumor was on her right eyebrow. After this lesion was excised, the patient presented a massive locoregional metastasis on the right parotid gland and the laterocervical lymph nodes. No distant metastases were detected. An incisional biopsy into the right parotid gland confirmed the diagnosis of MCC metastasis. No surgical treatment was prescribed because of the advanced stage of the disease. Spontaneous total regression on the parotid and the neck mass was observed within 3 months. This is the 15th case of spontaneous regression in total and the 14th case with a site of origin in the head and neck region.     

Lymphoepithelioma-like carcinoma of head and neck skin: a systematic analysis of 11 cases and review of literature

Lymphoepithelioma-like carcinoma of the skin (LELCS) is a rare tumor of unknown etiology, low malignant potential, and microscopic resemblance to undifferentiated nasopharyngeal carcinoma. Clinically, it presents as a flesh-colored firm nodule or plaque on the face, scalp, or shoulder of middle-aged to elderly individuals. Histologically, LELCS is composed of islands of enlarged epithelial cells with large vesicular nuclei surrounded and permeated by a dense lymphoplasmacytic infiltrate. LELCS exhibits immunoreactivity with high-molecular-weight cytokeratins and epithelial membrane antigen, indicating the epithelial origin. The differential diagnosis includes basal cell carcinoma, squamous cell carcinoma, lymphoma, pseudolymphoma, and Merkel cell carcinoma. We report 11 cases of LELCS of the head and neck region with discussion of the clinical, histopathologic, immunohistochemical, and therapeutic aspects of this rare cutaneous neoplasm. In addition, we systematically review and compare the findings with the previously published cases of LELCS. This study is the largest case series of LELCS reported in the English-language literature. It attempts to more clearly define the diagnostic criteria for LELCS. Its histomorphologic and immunophenotypic features help distinguish this tumor from similar-appearing malignancies, including metastatic nasopharyngeal carcinoma.     

腮腺区Merkel细胞癌一例报告及文献回顾

目的报告1例腮腺区Merkel细胞癌并进行文献复习。方法对1例MCC患者的临床病史,肿瘤组织的病理免疫组化表达及治疗过程进行回顾性分析,并结合国内外已发表有关MCC临床表现、治疗及预后进行回顾性总结分析。结果本例MCC患者表现为颌面部皮肤Merkel细胞癌,同时伴发腮腺内肿瘤,病理表现均为小细胞恶性肿瘤浸润性生长,免疫组化显示CK20（＋）、CK7（弱＋）;Syn（＋）;CgA（＋）;CD56（＋）。结论 MCC极罕见且进展快,可能有局部伴发或复发肿瘤,检查时对同时发现两个肿瘤应有所警惕。发生于颌面部时应注意与粘液囊肿、涎腺肿瘤、恶性淋巴瘤和恶性黑素瘤等鉴别。免疫组化在该病的诊断和鉴别诊断中具有重要价值。     

Gingival metastasis of Merkel cell carcinoma: a case report

An 82-year-old Caucasian man developed an ulcerated mass on the anterior mandibular gingiva. Five years previously he had been treated for a Merkel cell carcinoma (MCC) on his right cheek. Histopathologic examination showed small tumor cells with scanty cytoplasm, suggestive of malignancy. Immunohistochemical studies were performed with the use of nine antibodies. S-100 protein and leukocyte common antigen were helpful in ruling out melanoma and lymphoma. Pronounced reaction was shown for cytokeratin 20. a new histodiagnostic marker whose expression is almost entirely confined to Merkel cells, the gastric epithelium, and urothelium. The tentative diagnosis of metastasis of MCC was confirmed. Immunohistochemical studies are useful diagnostic aids in the establishment of the diagnosis of Merkel cell carcinoma.     

Neuroendocrine (Merkel cell) carcinoma of the oral mucosa: report of a case with immunohistochemical study and review of the literature

Merkel cell carcinoma (Mcc) is an uncommon and aggressive tumour with neuroendocrine features that occur predominantly in the head and neck region. The rarity of this tumour, especially when it arises in the oral mucosa, makes both early identification and standardisation of treatment difficult, particularly as regards complementary treatment. The availability of monoclonal antibodies with restricted specificity for some antigens thought to be related to neuroendocrine carcinomas, such as Merkel cell carcinoma, and ultrastructural studies offer some new leads to investigation. This has allowed, a greater number of these tumours to be discovered, thereby increasing the chances of effective management. A case of Mcc of the floor of the mouth is reported, together with the results of cytokeratin, neuron specific enolase and chromogranin immunohistochemistry.     

An update on the current management of head and neck mucosal melanoma

Primary mucosal melanomas of the head and neck are rare and aggressive tumours that arise in the nasal cavity, paranasal sinuses and more rarely in the oral cavity. The current treatment options include radical surgical resection with adjuvant external beam radiotherapy being offered in high‐risk patients. Although the latter can improve regional control, it does not reduce overall survival. Elective neck dissection is recommended for nodular oral mucosal melanoma, but its role in the clinically node negative neck is controversial. Systemic therapies including the use of tyrosine kinase inhibitors for tumours with c‐KIT mutations are suitable for patients with advanced loco‐regional and/or metastatic disease, but current results are variable. Patients with head and neck mucosal melanoma have a poor prognosis due to the high incidence of metastatic disease. This review assesses the latest evidence in the diagnosis and management of primary oral and head and neck mucosal melanoma including details of systemic therapies.     

Merkel cell carcinoma of the face. Case report and review of the literature

Merkel cell carcinoma of the skin has only recently been described. From the literature 115 cases are analysed. This carcinoma is most probably far more common than would be assumed from the few publications presently available. Between 40 to 50% of tumours are found in the head and neck area. Clinically the tumour presents as a typical bluish red firm intracutaneous nodule with the overlying skin intact, and sometimes malignant melanoma-like intracutaneous satellites. Regional lymph node metastasis is frequent and the five year survival rate, although not yet available, may well be about 50% or less. Clinical diagnosis is of paramount importance, as final diagnosis is only confirmed by electron microscopy and routine light microscopy leaves a wide range of differential diagnoses. In our case all typical characteristics are present. A cervicofacial flap which utilizes the abundant cervical skin for direct closure of the secondary defect in a U-Y manner was used to cover the primary defect. The flap is based on the preauricular area. Advantages and indications for the cervicofacial as opposed to Esser's cheek rotation flap are discussed.     

Pulmonary lymphangitic carcinomatosis from head and neck squamous cell carcinoma

Pulmonary lymphangitic carcinomatosis (PLC) secondary to mucosal head and neck squamous cell carcinoma (HNSCC) is extremely rare, difficult to diagnose in the pre-symptomatic phase, and is rapidly fatal. We describe two cases of fatal PLC secondary to squamous cell carcinoma in whom a review of pre-treatment imaging (computed tomography of the chest) changes reported as unspecific were retrospectively felt to be consistent with pre-symptomatic PLC. Case 1, a 73-year-old male with T2N2bMx poorly differentiated squamous cell carcinoma of the right tonsil, died 6 weeks after chemoradiotherapy with curative intent. Case 2, a 65-year-old female with T4aN2bMx of the right body of the mandible, died within 6 weeks of radical surgery including free tissue transfer. A review of the literature showed that PLC secondary to HNSCC occurs in an older cohort of patients: mean age 69 years vs. other tumour groups 50 years. PLC secondary to HNSCC can behave in distinctly different ways, demonstrating similarity to either gastric adenocarcinoma or bronchogenic squamous cell carcinomas.     

Merkel cell carcinoma of the upper eyelid: presentation and management

Merkel cell carcinoma (MCC) is a rare and potentially aggressive neuroendocrine tumour. The authors describe a unique presentation of a 4.5 cm wide MCC of the upper lid in a 73-year-old female. After total upper lid resection, immediate reconstruction was achieved by a full-thickness lower-lid transposition flap based on the lower lateral palpebral artery. At the 3 year follow-up the patient is free from disease and the reconstructive result is satisfactory both functionally and aesthetically.     

Cavernous sinus metastasis from oropharyngeal squamous cell carcinoma

Metastasis to the cavernous sinus from head and neck cancer is uncommon and has been previously reported by a few authors. It is usually a late manifestation of the primary tumor and may be the first evidence of a widespread dissemination of the disease. Main clinical findings are those related with involvement of cranial nerves III to VI as they pass through the cavernous sinus. Although diagnosis may be difficult, the appearance of clinical and radiological findings of cavernous sinus involvement in a context of head and neck cancer must alert us about an intracranial metastatic infiltration. In most cases treatment is palliative with radiotherapy and/or chemotherapy. The prognosis of this entity is poor, with survival of a few months. We present the case of cavernous sinus metastasis from oropharyngeal squamous cell carcinoma and review the literature about the clinical presentation and management of this rare entity.     

Verrucous carcinoma of the oral cavity: a clinico-pathologic appraisal of 133 cases in Indians

Introduction

Verrucous carcinoma (VC), a rare variant of squamous cell carcinoma is an established entity with distinctive morphology and specific clinical behavior. To date, only a small series of head and neck verrucous carcinomas have been reported in the literature.

Materials and methods

The present study evaluated 133 cases of verrucous carcinoma for the age, sex, site of involvement, duration of disease at the time of diagnosis, associated habits and common presenting symptoms, presence of other mucosal lesions, recurrence, and the histopathology.

Results and discussion

Verrucous carcinoma accounted for 16.08% among oral squamous cell carcinoma compared to 2–12% reported in the literature. VC was more common in males with greater predilection to buccal mucosa due to widespread use of tobacco chewing in Indian scenario. Age distribution was lower as compared to other studies with prominence in the fifth decade. Mandibular involvement was more frequent as compared to those in literature.

Conclusion

Development of recurrence following radiotherapy in few cases supports anaplastic changes by radiotherapy.