Metastatic cutaneous squamous cell carcinoma to the parotid: the role of surgery and adjuvant radiotherapy to achieve best outcome

Background: Australia has the highest incidence of cutaneous squamous cell carcinoma in the world. The majority of lesions occur in the head and neck with metastases to the parotid gland lymph nodes reflecting an uncommon, but aggressive, manifestation. Parotidectomy ± neck dissection followed by adjuvant radiotherapy should be considered as best practice. Methods: Between 1983 and 2000, seventy-four patients were treated for metastatic cutaneous squamous cell carcinoma to the parotid with surgery and adjuvant radiotherapy at Westmead Hospital, Sydney. Relevant data were extracted from patient files and a prospectively maintained database. Patterns of relapse and outcome were analysed. Results: Median age at diagnosis was 65 years (34−93 years) in 63 men and 11 women. Median follow-up duration was 41 months (12−188 months). All patients underwent parotidectomy with 52 undergoing a simultaneous neck dissection. Twelve patients required sacrifice of the facial nerve (4) or one or more branches (8). All received adjuvant radiotherapy to the parotid region with 56 also receiving radiotherapy to the ipsilateral neck. Despite treatment, 24% developed locoregional recurrence, with a median time to relapse of 7.5 months. The most common site for recurrence was the treated parotid region and upper neck. Most relapsed patients died. No variable independently predicted for locoregional recurrence on multivariate analysis. The 5-year absolute and cause-specific survival rates were 58% and 72%, respectively. Conclusion: Parotid gland lymph node metastases from cutaneous squamous cell carcinoma are associated with a high rate of recurrence and cause-specific mortality despite current best practice (surgery and high dose adjuvant radiotherapy). The role of more aggressive surgery, altered fractionation or chemotherapy to enhance locoregional control remains unclear.     

YAP1-MAML2-Rearranged Poroid Squamous Cell Carcinoma (Squamoid Porocarcinoma) Presenting as a Primary Parotid Gland Tumor

Porocarcinoma (synonym: malignant eccrine poroma) is a rare aggressive carcinoma type with terminal sweat gland duct differentiation. The squamous variant of porocarcinoma is even less frequent and might be indistinguishable from conventional squamous cell carcinoma (SCC). We herein describe the first case of a carcinoma presenting as a primary parotid gland malignancy in a 24-year-old male without any other primary tumor. Total parotidectomy and neck dissection were performed followed by adjuvant chemoradiation. The patient remained alive and well 10 months after diagnosis. Histology showed keratinizing SCC infiltrating extensively the parotid gland with subtle poroid cell features. Oncogenic HPV infection was excluded by DNA-based testing. NGS analysis using the TruSight RNA fusion panel (Illumina) revealed a novel YAP1-MAML2 gene fusion. This gene fusion was reported recently in a subset of cutaneous porocarcinoma and poroma. This case of poroid SCC (or squamoid porocarcinoma) adds to the differential diagnosis of SCC presenting as parotid gland tumor and highlights the value of molecular testing in cases with unusual presentation.Electronic supplementary materialThe online version of this article (10.1007/s12105-020-01181-9) contains supplementary material, which is available to authorized users.     

Understanding primary parotid squamous cell carcinoma – A systematic review

IntroductionThe true incidence of primary parotid squamous cell carcinoma (SCC) is unknown and likely overestimated in the literature. The aim of this systematic review is to examine the diagnosis, aetiology and incidence of parotid SCC by analysing studies evaluating primary parotid SCC.MethodsA systematic search of Medline, EMBASE and Cochrane library was performed. A narrative synthesis was done.ResultsA total of 14 observational retrospective studies on primary parotid SCC were included. There are currently no standard criteria for ascertainment of primary parotid SCC. Primary parotid SCC is thought to be due to squamous metaplasia within the ductal epithelium and subsequent invasive squamous carcinoma. Histological features that favour primary disease includes SCC confined to parotid parenchyma with no direct communication to the skin and the absence of mucin. Incidence of primary parotid SCC varied from 1.54 to 2.8 cases per million person-years. Around 30%–86% of patients recorded to have primary parotid SCC on clinical records, when scrutinised, were in fact secondary to parotid lymph node involvement following regional advancement from skin or upper aerodigestive tract SCC.ConclusionPrimary parotid SCC is rare and it is currently a diagnosis of exclusion. Thorough clinical assessment including endoscopy, preoperative imaging and the scrutiny of histopathological findings allow for differentiation between primary and secondary SCC within the parotid. This thus affects both initial treatment and subsequent follow-up.     

Localized carcinoma of the external ear is an unrecognized aggressive disease with a high propensity for local regional recurrence.

Management problems in patients with recurrent squamous cell carcinoma (SCC) of the external ear (pinna) have prompted a review of the management and treatment outcomes of patients who present with localized disease. Forty patients were seen over a 15-year period (1972 to 1991). Thirty-six were men, and 4 were women, with an age range from 43 to 93 years (average age: 71 years). Presenting TNM status was stage 0 in 2 patients, stage I in 15 patients, stage II in 13 patients, stage III in 2 patients, stage IV in 4 patients, and unknown stage in 4 patients. Thirty-six patients had clinically negative nodes at presentation (N0), and 4 had palpable nodes (N+). The primary treatment was local excision in 13 patients, Mohs' micrographic surgery in 16 patients, local excision plus external beam radiotherapy in 4 patients, and radical resection (parotidectomy/neck dissection/mastoidectomy) with or without radiotherapy in 5 patients. Two patients with stage IV disease died after diagnosis and prior to treatment, and two other patients with stage IV disease received palliative chemotherapy. Twenty patients developed recurrence from 2 months to 8 years. It included nine local recurrences, eight regional recurrences (parotid/neck/mastoid), and three distant metastases (lung or brain). After treatment of the recurrences in 20 patients, 8 are alive 15 months to 16 years later, 2 patients died of other diseases, and 10 patients died of SCC. The recurrences were managed by reoperation, radiotherapy, or chemotherapy. From the results of this study, we conclude that localized carcinoma of the external ear has a high propensity for local and regional failure and merits more aggressive treatment of the primary lesion and elective treatment of the regional lymph nodes and parotid gland in high-risk patients.     

Head and neck squamous cell carcinoma metastatic to the orbital apex

Primary squamous cell carcinoma of the head and neck most commonly metastasizes to the lymph nodes, lung, bone, and liver. Many other rare sites of metastatic disease have been reported. To date, metastatic squamous cell carcinoma of the head and neck to the orbital apex has not been described. Presented are two cases, one tonsil and one parotid primary with metastatic disease to the orbital apex. Many tumors have been found to metastasize to the eye and orbit, but head and neck neoplasms are rarely reported. A review of the literature is presented in addition to the detailed case reports with their radiologic findings and clinical course. Surgical resection followed by postoperative radiotherapy appears the treatment of choice at this time.     

Head and Neck Squamous Cell Carcinoma Metastatic to the Orbital Apex

Primary squamous cell carcinoma of the head and neck most commonly metastasizes to the lymph nodes, lung, bone, and liver. Many other rare sites of metastatic disease have been reported. To date, metastatic squamous cell carcinoma of the head and neck to the orbital apex has not been described. Presented are two cases, one tonsil and one parotid primary with metastatic disease to the orbital apex. Many tumors have been found to metastasize to the eye and orbit, but head and neck neoplasms are rarely reported. A review of the literature is presented in addition to the detailed case reports with their radiologic findings and clinical course. Surgical resection followed by postoperative radiotherapy appears the treatment of choice at this time.     

Patterns of lymph node spread of cutaneous squamous cell carcinoma of the head and neck

BACKGROUND: Among patients with cutaneous squamous cell carcinoma (SCC) of the head and neck, recent studies have shown that those with involvement of the parotid gland also have a high incidence of neck node involvement. Treatment of the neck by either surgery or radiotherapy is therefore recommended among patients with parotid SCC, even if clinical examination is negative. The aim of this study was first to analyze patterns of metastatic spread in the parotid and cervical lymph nodes and then to correlate the pattern of involved nodes with the primary cutaneous site in order to guide the appropriate extent of surgery, should neck dissection be used to treat the neck in patients with parotid SCC. METHODS: A cohort of 209 patients with cutaneous SCC of the head and neck and clinically evident regional metastatic disease was reviewed retrospectively from 3 Australian institutions. The distribution of involved nodes was obtained from pathology reports; the anatomic sites of primary cutaneous cancers were then correlated with these findings. RESULTS: Among 209 patients, 171 (82%) had clinical parotid involvement. Of these, 28 had clinical neck disease, whereas 143 had parotid disease alone. Thirty-eight (18%) patients had neck disease only. A total of 199 patients were treated surgically, whereas 10 received radiotherapy alone. Surgery included 172 parotidectomies and 151 neck dissections (93 of which were elective). Primary sites were cheek (21.7%), pinna (20.4%), temple (15.8%), forehead (15.8%), postauricular region (5.9%), neck (5.3%), anterior scalp (5.3%), posterior scalp (3.3%), periorbital (3.3%), nose (2.6%), and chin (0.6%). Among pathologically positive necks, level II was most frequently involved (79%). Level IV (13%) and level V (17%) were only involved in extensive lymph node disease, the exception being for isolated level V metastases from the posterior scalp. CONCLUSIONS: Primary sites were mainly localized to the lateral aspect of the head. Among patients with cutaneous SCC involving the parotid and neck, level II was the most commonly involved neck level. The distribution of involved nodes suggests that in a patient with parotid involvement and a clinically negative neck with an anterolateral primary, a supraomohyoid neck dissection, always including the external jugular lymph node(s) would be appropriate. In the case of a posterior primary, level V should be dissected as well. In patients with parotid SCC and a clinically positive neck, a comprehensive neck dissection is recommended.     

Squamous cell carcinoma of the renal pelvis after curative retroperitoneal radiotherapy for seminoma

We report the case of a 71-year-old male who presented with squamous cell carcinoma of the renal pelvis in a solitary functioning kidney, 34 years after orchidectomy and adjuvant retroperitoneal radiotherapy for stage II seminoma. This rare second malignancy occurred in the radiation treatment field. Second malignancies are an uncommon but serious sequela of radiotherapy, with potential for significant health problems in patients with complete remission of primary disease. To our knowledge, this is the first report of squamous cell carcinoma of the renal pelvis occurring after radiation treatment.     

Non-functional recurrent pituitary adenoma with intracranial metastasis–Pituitary carcinoma: A case report and review of the literature

IntroductionPituitary carcinomas are rare, with only a few case reports to date. We present a null cell type non-functioning pituitary carcinoma (NFPC) with intracranial metastases and a review of the literature.Case reportA 56-year-old male with a history of an aggressive pituitary adenoma was admitted. Initial MRI highlighted a large intracranial mass with leptomeningeal involvement, simulating meningioma. Based on his previous pathology report of the sellar mass, a diagnosis of null cell type non-functioning pituitary carcinoma has been made.ConclusionsAn aggressive recurrent pituitary tumor with suprasellar and/or cavernous sinus invasion is the main characteristics of the NFPC. Single or multiple enhancing dural-based mass(es) mimicking meningioma is the most common MRI finding. The proof of malignancy is the same histopathological features of the recurrent aggressive pituitary tumor in the metastases. The histology alone is not distinctive in terms of malignancy. Most patients require a combined surgery, radiotherapy and chemotherapy.     

Squamous and basal cell cancers directly invading major salivary glands

Epidermoid carcinoma of the skin of the head and neck may uncommonly involve the parotid gland by either direct extension or metastases to the parotid lymph nodes. The parotid gland contains a rich network of superficial and deep nodes, draining a large area of the facial region, with the preauricular, cheek, ear, and eyelid dominating. Few patients with direct parenchymal invasion of the parotid gland by a simultaneously existing squamous or basal cell carcinoma were reported. We could find no report discussing direct tumoral invasion into the submandibular salivary gland. Three patients with squamous cell carcinomas and 2 with basal cell carcinomas of the skin directly involving the underlying salivary glands are presented. The few authors discussing this subject concur that treatment should include resection of the primary tumor along with parotidectomy. Elective neck dissection and irradiation are proposed. The course of disease, treatment, and survival of our patients are discussed.     

Unusual Merkel cell carcinoma in a renal transplant recipient: case report and review of the literature

Merkel cell carcinoma (MCC) is an uncommon and aggressive neuroendocrine primary skin cancer known for its high propensity for local recurrence and distant metastases. There is no consensus regarding the optimal therapeutic approach, and the relative roles of surgery, radiotherapy and chemotherapy are still controversial. MCC generally affects elderly patients in areas of actinically damaged skin. Several studies suggest that a more aggressive course is observed in immunocompromised patients such as organ transplant recipients. Clinically, MCC usually appears as a rapidly growing, dome-shaped and solitary nodule. More than half of these tumours occur in the head and neck, and can become a challenge for the plastic and reconstructive surgeon. An unusual case of this cutaneous malignancy is presented in a renal transplant recipient. The tumour was located in the medial canthus of the eye. Tumour resection was performed and a reverse flow pre-auricular island flap and a forehead flap were used for reconstruction.     

The treatment of squamous cell carcinoma of the tonsil with neck node metastases

BACKGROUND: Patients with tonsillar carcinoma and neck nodes seen at the clinic are not an uncommon occurrence in head and neck practice. Over the years, treatment has ranged from radical jaw neck dissection to radical neck dissection for the nodes and primary radiotherapy to the primary site. Much controversy exists as to which treatment modality yields the best survival. Certainly, surgery to the oropharynx leads to gross morbidity, with problems of swallowing, speech, and cosmesis, although it has been claimed that radiotherapy with neck dissection yields a lower cure rate. METHODS: We investigated a retrospective series of 96 patients all of whom had squamous cell carcinoma of the tonsil and associated lymph node metastases. Of these, 44 primary tumors were treated with surgery and 52 with irradiation. All 44 patients in the surgery group had a radical neck dissection, as did all but 12 in the radiotherapy group. RESULTS: Of the tabulations, patients in good general condition were more likely to receive primary surgery. Overall cause-specific survival for all patients was 69%. Multiple logistic regression revealed no associations; thus, the radiotherapy and surgery groups were well matched. Five-year actuarial survival for those having irradiation was 74%. The five-year survival for the group receiving surgery was 63% (p =.4372). This lack of difference between survival for surgery and radiotherapy was confirmed using Cox's proportional hazards model. CONCLUSION: We conclude that tonsillar carcinoma with lymph nodes can be safely treated by applying appropriate radiotherapy to the tonsillar region and treating the neck with radical surgery, if the disease is more than N1.     

Intracranial metastases in patients with squamous cell carcinoma of the head and neck.

BACKGROUND: Intracranial metastases are rarely clinically diagnosed in patients with head and neck squamous cell carcinoma. Only 7 patients with metastases to the cavernous sinus from head and neck squamous cell carcinomas have been reported. METHODS: A retrospective study revealed 13 patients with intracranial metastases of head and neck squamous cell carcinoma. In a 53-year-old woman a cavernous sinus metastasis of a laryngeal carcinoma was histologically diagnosed by using a CT-guided surgical navigation system and was treated with stereotactic radiotherapy. RESULTS: The mean survival was 4.3 months. Predictive factors for longer survival were absence of extracranial disease, age younger than 60 years, and treatment with radiotherapy. CONCLUSIONS: The prognosis for patients with intracranial disease is poor. The current development of computer-assisted stereotactic navigation and stereotactic radiotherapy may facilitate surgical diagnostic exploration and improve treatment, especially in patients without extracranial disease.     

Merkel cell carcinoma of the head and neck: Is adjuvant radiotherapy necessary?

BACKGROUND: Controversy exists regarding the optimal management of patients with Merkel cell carcinoma. The primary aim of this study was to determine whether combined treatment with surgery and radiotherapy improves outcome in a multi-institutional cohort of patients with Merkel cell carcinoma of the head and neck. The secondary aims were to determine by stage, which patients derive benefit from combined therapy and to identify predictors for survival on multivariable analysis. METHODS: A retrospective analysis of 110 patients with Merkel cell carcinoma of the head and neck was performed. Data were collected from 3 tertiary care institutions (Westmead Hospital, Sydney, Australia; Princess Margaret Hospital, Toronto, Canada; Royal Prince Alfred Hospital, Sydney). There were 78 males and 32 females, median age was 70 years, and mean follow-up of survivors was 2.3 years. Sixty-six patients underwent combined treatment, and 44 patients had either surgery or radiotherapy alone. Analysis by stage was performed using 2 staging systems. RESULTS: Local and regional control at 5 years was 84% and 69%, respectively. Combined treatment improved both local (p = .009) and regional control (p = .006). Overall and disease-specific survival at 5 years was 49% and 62%, respectively. Combined treatment was associated with significantly better disease-free survival on univariable analysis (p = .013) When analyzed by stage, patients with stage IIb (primary >1 cm, node negative) disease who underwent combined treatment had improved disease-free (p = .005) and disease-specific survival (p = .035). Predictors of survival on multivariable analysis were age >70 years (HR 6.19, p < .001), primary tumor size >1 cm (HR 7.55, p < .001), number of nodal metastases divided into none, 2 (HR 3.71 per stratum, p < .001). When analyzed with age and disease stage, treatment modality trended toward significance as a predictor of disease-specific (p = .081) and overall survival (p = .076). Disease stage was the most powerful independent predictor on Cox regression (HR 5.43 per stratum, p < .001). CONCLUSIONS: Merkel cell carcinoma is an aggressive cutaneous malignancy. Age and disease stage are the most important predictors of survival. Combined surgery and radiotherapy improves both locoregional control and disease-free survival. Patients with stage II disease appear to derive the greatest benefit from adjuvant radiotherapy, including improved disease specific survival.     

Improved Staging of Cervical Metastases in Clinically Node-Negative Patients With Head and Neck Squamous Cell Carcinoma

Background: The management of the N0 neck in oral and oropharyngeal cancer is often determined by the risk of metastases related to features of the primary tumor. Where the risk of metastases is >20%, elective neck dissection (END) has been advocated. This study reviewed clinical staging, surgical staging, pathologic staging, and histopathologic parameters to determine the prediction of nodal metastases and micrometastases in patients with head and neck squamous cell carcinoma.Methods: A prospective series of 61 clinically neck node–negative patients undergoing surgical resection of a T1/2 intraoral or oropharyngeal invasive squamous cell carcinoma and surgical staging of the neck, with sentinel node biopsy (SNB) alone or SNB-assisted END, between June 1998 and March 2002 were included in this study.Results: Pathologic upstaging of the clinically N0 neck occurred in 27 (44%) of 61 patients. Routine pathology with hematoxylin and eosin upstaged disease in 22 of 27 patients (sensitivity of 81%). Five patients with micrometastasis were staged pN1mi after stepped serial sectioning and immunohistochemistry. Tumor thickness, a noncohesive invasive front, and perineural and bone invasion were all histological predictors for cervical metastases. Five patients with micrometastases were staged pN1mi.Conclusions: Both clinical staging and routine pathologic staging underestimate the presence of nodal metastases. Staging with either SNB alone or SNB-assisted END shows promise in the management of the N0 neck by identifying patients with micrometastases (pN1mi).     

Lymph node metastasis in squamous cell carcinoma of the oral cavity: correlation between histologic features and the prevalence of metastasis.

A retrospective study was made of the correlation between preoperative clinical or histologic findings and the prevalence of lymph node metastasis in 60 patients with squamous cell carcinoma of the oral cavity who had histologically confirmed neck metastasis. Of these 60 patients, 39 with clinically N+ necks underwent immediate therapeutic neck dissection, and 21 whose necks were initially N0 but progressed to N+ during observation underwent subsequent therapeutic neck dissection. The primary site, TNM staging, histologic grade of malignancy of biopsy specimen, and location and number of histologically positive lymph nodes were reviewed in each case. The results were as follows: (1) The prevalence of neck metastasis was not significantly correlated with primary site and T stage; however, there was an apparent correlation between histologic grade of malignancy and the prevalence of neck metastasis. Patients with grade I-II histologic malignancy showed limited metastases that involved lymph nodes in levels I-II. On the other hand, patients showing grade III-IV histologic malignancy often had metastases that extended beyond level III, regardless of T stage. These results suggest that histologic grade of malignancy, as well as clinical features, must be taken into consideration when deciding whether supraomohyoid neck dissection is indicated. (2) The group that underwent subsequent neck dissection exhibited less advanced neck metastasis and a better prognosis than the group which underwent immediate neck dissection. These findings show that if they are closely followed up, it is possible to delay neck dissection in N0 patients until a neck metastasis is detected.     

Role of planned neck dissection for advanced metastatic disease in tongue base or tonsil squamous cell carcinoma treated with radiotherapy

OBJECTIVE: At the conclusion of this article, the reader should be able to discuss the need for planned neck dissection for advanced cervical diseases in the tongue base and tonsil cancer after treatment with radiotherapy. BACKGROUND: In the past 5 years, we have treated patients with squamous cell carcinoma of the tonsil and tongue base with radiotherapy as the primary therapeutic modality. A planned complete neck dissection was performed on all patients with N2 or greater cervical disease regardless of response to radiotherapy. Composite resection was performed when there was persistent disease at the primary site. Although the "radiation-first" therapeutic approach for tongue base and tonsil cancer is widely accepted, the planned neck dissection for neck metastases remans controversial. The objective of the study was to determine the validity of planned neck dissection after radiotherapy for N2 disease. METHODS: Medical records of patients with primary squamous cell carcinoma of the tongue base and tonsil with neck metastasis staged N2 or greater were reviewed. Between 1994 and 1999, 36 such patients were treated with curative radiation therapy. Response was assessed 6 to 8 weeks after completion of treatment with clinical examination and CT imaging. All patients underwent planned neck dissection. We reviewed the clinical and radiographic response of neck disease to radiotherapy as it correlated with the histopathologic findings. RESULTS: Of the 36 patients, 17 had clinical and CT evidence of persistent disease. In this group, 65% had pathologically confirmed diseases at surgery. Of the 9 patients with no evidence of disease on clinical examination, negative biopsy at the primary site, and a negative CT scan, 33% (three of nine) still had residual disease in the neck dissection specimen. CONCLUSIONS: Positive findings on clinical examination and CT can predict the presence of malignancy after radiation therapy. However, a negative CT and clinical examination are limited in predicting a complete response. These data lend support to the role of planned neck dissection after radiotherapy of N2 neck disease.     

Cutaneous squamous cell carcinoma of the head and neck metastasizing to the parotid gland--a review of current recommendations

Cutaneous squamous cell carcinoma (SCC) of the head and neck may metastasize in up to 5% of patients, with the parotid lymph nodes the most frequent site for spread. Metastases frequently show delayed presentation after the primary cancer had been treated. The optimum treatment should be surgery followed by adjuvant radiotherapy, with an appropriate parotidectomy, and preservation of the facial nerve if not involved by tumor and treatment to the neck. In a clinically N0 neck, levels I to III should be cleared for facial primaries, levels II to III for anterior scalp and external ear primaries, and levels II to V for posterior scalp primaries. Approximate 5-year disease-specific survival (DSS) after treatment was 70% to 75%. Patients with immunosuppression, in particular transplant recipients, are at high risk of developing aggressive metastatic cutaneous SCC. Modifications of the staging systems have demonstrated the prognostic benefits of accurately staging parotid and/or neck nodal disease.     

Squamous cell carcinoma in an esophageal diverticulum below the aortic arch

INTRODUCTIONEsophageal diverticula frequently arise from pharyngoesophageal transition area, tracheal bifurcation and epiphrenic region. Carcinoma arising from esophageal diverticulum is rarely seen. We report a patient with a squamous cell carcinoma arising within an esophageal diverticulum below the aortic arch.PRESENTATION OF CASEA 70-year-old man was diagnosed to have a squamous cell carcinoma of the vocal cord with enlarged lymph nodes in the neck, as well as a squamous cell carcinoma arising within an esophageal diverticulum below the aortic arch. There have been no reported cases of esophageal cancer arising from a diverticulum below the aortic arch. Preoperative radiotherapy for the esophageal cancer and pharyngeal cancer was given, followed by surgery. The excised specimen of the esophageal diverticulum and its external appearance revealed that it lacked muscle fibers, with a type 0-IIa lesion arising from the diverticulum. Microscopic examination showed three lymph nodes at the superior mediastinum were positive for malignancy. Bilateral pleural dissemination was detected 7 months after esophagectomy.DISCUSSIONCancer arising from an esophageal diverticulum is mainly found at an advanced stage because of delayed diagnosis. The absence of muscularis propia may lead to early invasion. Thus, cancers within an esophageal diverticulum are considered to be at a more advanced stage than similar cancers arising elsewhere.CONCLUSIONFor detecting of cancer arising from an esophageal diverticulum, a high index of awareness is important. Delay in diagnosis makes surgical management difficult.     

c-met overexpression in supraglottic laryngeal squamous cell carcinoma and its relation to lymph node metastases

BACKGROUND: The c-met oncogene encodes the receptor for the hepatocyte growth factor/scatter factor (HGF/SF), which is known to have the effects of stimulation of cell motility, dissociation of epithelial sheets, invasion of cellular matrix, and induction of angiogenesis. Many studies in solid tumors have indicated a role for c-met and HGF/SF in the progression of the disease. METHODS: The expression of c-met in tissue specimens was studied by immunohistochemical examination in 60 patients with supraglottic laryngeal squamous cell carcinoma. Patients were chosen such that there were 30 with lymph node metastases in the neck and 30 without metastases. TNM staging, differentiation, lymphovascular and perineural invasion, and growth pattern for tumors were also recorded, and their relation to lymph node metastases was analyzed. RESULTS: Overexpression of c-met was observed in 90% of the cases at the primary site and in 83% of the cases with lymph node metastases in the neck. Lymphovascular invasion (P = 0.005) and the N stage (P = 0.001) were found to be related to lymph node metastases, but other variables-c-met overexpression, the T stage, perineural invasion, and growth pattern-were found to have no relation to lymph node metastases in multivariate analysis of the data with linear regression. CONCLUSIONS: c-met overexpression is observed in both the primary site and the neck in supraglottic laryngeal squamous cell carcinoma. We believe that it may have a role in the progression of malignancy, but we were unable to find a definite relation between c-met expression and lymph node metastases.