Benefit of postoperative chemoradiotherapy for patients with unknown primary squamous cell carcinoma of the head and neck

BACKGROUND: Postopertative adjuvant chemoradiotherapy recently became an established modality for patients with selected high-risk locally advanced head and neck cancers. The optimal treatment of unknown primary squamous cell cancer of the head and neck (SCCHN) continues to be controversial, since major randomized studies excluded those patients. METHODS: We conducted a retrospective review of patients treated during 1995 to 2002 for unknown primary SCCHN. All patients were treated with a neck dissection followed by concurrent high-dose cisplatin (100 mg/m(2)) and bilateral neck radiotherapy. RESULTS: Thirty-seven patients were identified with nodal disease distribution of N1 (5%), N2a (22%), N2b (41%), N2c (8%), N3 (22%), and Nx (3%). Modified neck dissection was done on the majority (30/37 = 81%) of patients. With a median follow-up of 42 months among the survivors, very few patients had regional recurrence (5%) or distant failure (11%), and 89% of patients were alive. The actuarial 5-year overall survival rate could not be estimated because there were no deaths beyond 20 months after surgery. Substantial yet acceptable acute and late morbidities were demonstrated in this cohort of patients. CONCLUSIONS: Postoperative chemoradiotherapy is of potential benefit to patients with unknown primary SCCHN by improving survival and reducing failures. This treatment warrants further prospective evaluation.     

Prostatic adenocarcinoma metastatic to the head and neck and the workup of an unknown epithelioid neoplasm

BACKGROUND: Epithelioid tumors in the head and neck are common and include both primary and metastatic lesions. For metastatic lesions, clinical factors, tumor location, and ancillary immunohistochemical studies must be taken into consideration to help the clinician and the pathologist determine the site of origin. One unusual, but important, primary tumor that can metastasize to the head and neck is carcinoma of the prostate (CAP). METHODS: The files of the University of Pennsylvania Department of Pathology were searched for cases of metastatic CAP. All slides were examined, and clinical information was obtained from the referring physician's patient charts. RESULTS: We describe 14 cases of metastatic CAP to the head and neck. Six patients had no history of CAP at the time of biopsy of the head and neck metastasis, and only eight patients had other widespread metastatic disease. Histologically, most of the tumors had epithelioid cells with prominent nucleoli and cribriform, solid, or infiltrating single cell growth patterns. PSA and PSAP immunohistochemical stains were positive in all cases. Seven of 12 patients with known follow-up are alive after radiation or hormonal therapy. CONCLUSIONS: These results demonstrate a fair prognosis with possible prolonged survival with metastatic CAP to the head and neck after appropriate diagnosis and subsequent hormone and radiation therapy. Given this survival advantage with treatment, it is critical to consider the diagnosis of metastatic CAP when evaluating a metastatic malignant epithelioid tumor in the head and neck of an elderly man.     

Prospective study of 18FDG-PET in the detection and management of patients with lymph node metastases to the neck from an unknown primary tumor. Results from the DAHANCA-13 study

BACKGROUND: The benefit of a complementary fluorodeoxyglucose-positron emission tomography (FDG-PET) scan to standard workup for carcinoma of unknown primary (CUP) and metastatic neck lesions was prospectively studied. METHODS: Sixty-seven patients underwent standardized diagnostic workup according to national guidelines including panendoscopies, multiple mucosal biopsies, and diagnostic CT/MRI scans. Median follow-up was 40 months (range, 2-65 months). RESULTS: In 60 eligible patients, FDG-PET indicated a primary tumor or metastatic disease in 30 patients (50%). Additional investigations confirmed a primary tumor in 18 patients: hypopharynx in 5, oropharynx in 5, nasopharynx in 2, lung in 1, axilla in 1, bone in 1, rectum in 1, as well as multiple metastatic lesions from CUP in 2 patients. In retrospect, MRI was able to detect 1 of the PET-detected primaries, leading to an overall detection rate of PET of 29% in CUP. A therapeutic change of treatment was made in 25% as a consequence of FDG-PET. PET before panendoscopy demonstrated fewer false-positive pathological foci. CONCLUSION: FDG-PET is a valuable tool in addition to conventional extensive workup in CUP and neck metastases. Consequently, FDG-PET is now recommended as an early diagnostic modality in the workup of these patients.     

Metastatic cutaneous squamous cell carcinoma of the scalp

Background: Metastatic cutaneous squamous cell carcinoma arising from the scalp, although relatively uncommon, is associated with a poor outcome. Older men with a history of baldness and actinic scalp lesions are particularly at risk. Methods: Between 1980 and 2005, 27 patients with metastatic cutaneous squamous cell carcinoma of the scalp were referred to the Head and Neck Cancer Service at Westmead Hospital, Sydney. Relevant data were extracted from a prospectively maintained database. Patterns of recurrence and outcome were analysed. Results: Median age at diagnosis was 70 years and median follow up was 45 months in 26 men and one woman. Ten primary (index) lesions were located on the midline scalp, 14 left sided and 3 right sided. Median lesion size was 18 mm and median thickness was 5.5 mm. The median time between treatment of the scalp primary and the development of nodal metastases was 8 months. In 10 patients, nodal metastases were present at the time of primary treatment. Fifteen patients developed parotid metastases (+cervical nodes in 7 of 15) and 12 developed cervical only metastases (5 of 12 level V). All patients underwent nodal surgery and most (75%) also received adjuvant radiotherapy. At the last follow up, 41% of patients had died from their disease. Median survival after relapse was 9 months and all patients experiencing relapse died with most (11 of 13) dying from metastatic disease. Conclusion: Patients with metastatic cutaneous squamous cell carcinoma of the scalp have a poor prognosis with most dying from regional relapse. Those treated with surgery and adjuvant radiotherapy had a better outcome.     

Contemporary management of lymph node metastases from an unknown primary to the neck: II. A review of therapeutic options

Although uncommon, cancer of an unknown primary (CUP) metastatic to cervical lymph nodes poses a range of dilemmas relating to optimal treatment. The ideal resolution would be a properly designed prospective randomized trial, but it is unlikely that this will ever be conducted in this group of patients. Accordingly, knowledge gained from retrospective studies and experience from treating patients with known head and neck primary tumors form the basis of therapeutic strategies in CUP. This review provides a critical appraisal of various treatment approaches described in the literature. Emerging treatment options for CUP with metastases to cervical lymph nodes are discussed in view of recent innovations in the field of head and neck oncology and suitable therapeutic strategies for particular clinical scenarios are presented. For pN1 or cN1 disease without extracapsular extension (ECE), selective neck dissection or radiotherapy offer high rates of regional control. For more advanced neck disease, intensive combined treatment is required, either a combination of neck dissection and radiotherapy, or initial (chemo)radiotherapy followed by neck dissection if a complete response is not recorded on imaging. Each of these approaches seems to be equally effective. Use of extensive bilateral neck/mucosal irradiation must be weighed against toxicity, availability of close follow‐up with elective neck imaging and guided fine‐needle aspiration biopsy (FNAB) when appropriate, the human papillomavirus (HPV) status of the tumor, and particularly against the distribution pattern (oropharynx in the majority of cases) and the emergence rate of hidden primary lesions (<10% after comprehensive workup). The addition of systemic agents is expected to yield similar improvement in outcome as has been observed for known head and neck primary tumors. Head Neck, 2013     

Role of squamous cell carcinoma antigen 1 expression in the invasive potential of head and neck squamous cell carcinoma

BACKGROUND: Serine proteases have important roles in tumor invasion and metastasis, and their inhibitors, serine protease inhibitors (serpins), are attractive targets for therapeutic strategies. On chromosome 18q21, there is a cluster of serpins: maspin, headpin, and squamous cell carcinoma antigen 1 (SCCA1)/SCCA2. Others and we have reported that the expression of these serpins is down regulated in head and neck squamous cell carcinoma (HNSCC) cells compared with normal squamous epithelial cells. In this study, we hypothesized that expression of SCCA1 is biologically disadvantageous to HNSCC cells. METHODS: HNSCC cell lines were transfected with a mammalian expression vector with SCCA1 cDNA. In vitro proliferation, migration, or invasive potential (matrigel assay) of the transfectants were assayed. In addition, the in vivo growth and invasion was analyzed using the floor-of-mouth model of nude mice. RESULTS: SCCA1 expression did not alter the in vitro growth rate of established HNSCC cells. However, SCCA1 expression significantly inhibited the in vitro invasion in matrigel assays. Furthermore, the in vivo growth and invasion in nude mice was also inhibited by SCCA1 expression. CONCLUSIONS: Overexpression of SCCA1 in a HNSCC cell line inhibited its invasive potential. Loss of expression of the serpin SCCA1 may play a role in the malignant progression of HNSCC.