Head and neck carcinoma of unknown primary

In adult cervicofacial pathology, carcinoma of unknown primary is defined as lymph-node metastasis the anatomic origin of which is not known at the time of initial management. It constitutes up to 5% of head and neck cancers. Presentation may suggest benign pathology, delaying and confusing oncologic treatment. Diagnostic strategy in cervical lymph node with suspicion of neoplasia requires exhaustive work-up to diagnose malignancy and, in 45% to 80% of cases, depending on the series, to identify the primary site. Histologic types comprise squamous cell carcinoma, thyroid carcinoma, adenocarcinoma, neuroendocrine carcinoma and undifferentiated carcinoma. Association is sometimes found with human papilloma virus or Epstein Barr virus, guiding treatment. The objective of the present study was to provide clinicians with the necessary diagnostic tools, based on the current state of clinical, imaging and pathologic knowledge, and to detail treatment options.     

Head and neck squamous cell carcinoma from an unknown primary site

Background

The purpose of this study is to present our experience treating patients with squamous cell carcinoma (SCC) from an unknown head and neck primary site and to determine whether a policy change eliminating the larynx and hypopharynx from the radiotherapy (RT) portals has impacted outcome.

Methods

One hundred seventy-nine patients received definitive RT with or without a neck dissection for SCC from an unknown head and neck primary site. RT was delivered to the ipsilateral neck alone or both sides of the neck and, usually, the potential mucosal primary sites. The median mucosal dose was 5670 cGy. The median neck dose was 6500 cGy. One hundred nine patients (61%) received a planned neck dissection.

Results

Mucosal control at 5 years was 92%. The mucosal control rate in patients with RT limited to the nasopharynx and oropharynx was 100%. The 5-year neck-control rates were as follows: N₁, 94%; N_2a, 98%; N_2b, 86%; N_2c, 86%; N₃, 57%; and overall, 81%. The 5-year cause-specific survival rates were as follows: N₁, 94%; N_2a, 88%; N_2b, 82%; N_2c, 71%; N₃, 48%; and overall, 73%. The 5-year overall survival rates were as follows: N₁, 50%; N_2a, 70%; N_2b, 59%; N_2c, 45%; N₃, 34%; and overall, 52%. Eleven patients (7%) developed severe complications.

Conclusion

RT alone or combined with neck dissection results in a high probability of cure with a low risk of severe complications. Eliminating the larynx and hypopharynx from the RT portals did not compromise outcome and likely reduces treatment toxicity.     

Squamous cell carcinoma metastatic to the neck from an unknown head and neck primary site

Squamous cell carcinoma metastatic to the neck from an unknown head and neck primary site is relatively uncommon and presents a challenging diagnostic and therapeutic dilemma. Diagnostic evaluation includes fine-needle aspiration of the neck mass, chest roentgenography, computed tomography, and/or magnetic resonance imaging of the head and neck, followed by panendoscopy and biopsies. The primary tumor will be detected in approximately 40% of patients; approximately 80% of cancers are located in the base of the tongue or tonsillar fossa. Management options include treatment of the neck alone or both sides of the neck and the potential head and neck primary sites. The latter approach is associated with better long-term control above the clavicles. The 5-year survival rate is approximately 50% after treatment and is influenced by the extent of neck disease. In this article, we review the pertinent literature.     

Advances in the diagnosis of unknown primary carcinoma of the neck

The diagnosis of carcinoma of unknown primary is set, when histologically the neck metastases are confirmed but the primary focus is not possible to be found or occurs during the follow-up. The CUP-nodes constitute 2-20% of all neck metastases in laryngological entities. The squamous cell carcinoma or anaplastic carcinoma recognized in the neck nodes suggest, that the primary focus is localised in the head and neck region. AIM: The schedule of diagnostic procedure aiming at finding the primary focus in CUP-syndrome is presented. The knowledge of carcinoma cells spreading paths between particular neck regions is crucial for effective diagnostics of tumor localization in upper aerodigestive tract. RESULTS: Among 3320 oncological patients treated between 1993-2003 in Department of Otolaryngology, Head Neck Oncological Surgery 32 were diagnosed as CUP syndrome. In 17 patients the primary localisation was revealed during the follow-up period in: nasopharynx, palatine tonsil, hypopharynx, testis and breast. In 15 patients the primary focus was never found. The radical neck dissection followed by radiotherapy or chemotherapy was performed in patients with CUP. In cases when primary tumor was found, the radical surgery or radiotherapy was additionally applied.     

Squamous cell carcinoma. Metastasis to the neck from an unknown or undiscovered primary

With an unknown or occult primary cancer, the clinical presentation can be either undiagnosed lump or lumps in the neck that has been biopsied and diagnosed as metastatic cancer on the basis of the histopathologic findings.     

Metastatic endometrial carcinoma of the neck

We report a case of metastatic endometrial carcinoma of the neck. A patient with a past medical history of squamous cell carcinoma of the larynx, breast carcinoma and endometrial carcinoma presented with a neck mass. Fine needle aspiration cytology (FNAC) showed this to be a poorly differentiated carcinoma with squamoid features and thus a potentially curative neck dissection was performed. Histology of the mass showed a clear cell endometrial carcinoma. Metastatic gynacecological malignancies to the head and neck are rare and this is the first reported case of metastatic endometrial carcinoma in the neck.     

Metastatic squamous cell carcinoma in cervical lymph nodes from an unknown primary tumour: prognostic factors

The aim of this retrospective review is the study of the prognostic factors related to cervical metastases of squamous cell carcinoma from an unknown primary tumour. Sixty-seven patients were selected and surgery and postoperative radiotherapy was the treatment used. Nineteen tumours were subsequently found (27%). The 5-year actuarial survival rate of all patients was 22%. Survival rates were significantly related to lymph node stages and to the histological degree of differentiation. Nevertheless, actuarial survival rates were not related to the appearance of the primary tumour (P = 0.07). In our series, the single most important prognostic factor was the neck stage. The value close to statistical significance observed when the primary tumour subsequently appeared (P = 0.07), suggests that this could worsen the prognosis.     

Diagnosis and management of carcinoma of unknown primary in the head and neck

Carcinoma of unknown primary is defined as the histological diagnosis of metastasis without the detection of a primary tumor. In the literature, the incidence of CUP in all patients with a malignant disease is said to be between 3% and 15%. The most frequent histopathological results of CUP metastases are adenocarcinoma, followed by undifferentiated carcinoma and squamous cell carcinoma. In this retrospective investigation the clinical records of 167 patients were studied. All patients had been admitted and treated for cervical CUP at the Department of Otorhinolaryngology of the Grosshadern Clinic from 1979 to 1998. Cervical swelling was the first noted symptom in all cases, followed by pain and dysphagia. The study group comprised 134 men and 33 women with an average age of 55 years at admission. Squamous cell carcinoma (n=123) was the predominant histopathological finding of the cervical lymph nodes. During the 10-year follow-up, a primary tumor was detected in 36 (21.5%) of the 167 initially diagnosed CUP patients. In over 90% of these cases the tumor was localized in the head and neck region. The most frequent origin of the tumor was the tonsilla palatina (n=7). Neck dissection and additional postoperative radiotherapy was performed in 118 (70.7%) of the 167 CUP patients. Primary radiotherapy was the treatment of choice in 28 patients; eight patients received combined radio-chemotherapy as the primary treatment and seven patients were treated with chemotherapy alone. Six patients had no treatment. Comparison of different treatment protocols revealed a significant difference in patient survival: in comparison with primary radiotherapy alone or neck dissection and postoperative radiotherapy, the survival rate improved significantly in patients that received a bilateral tonsillectomy in addition to neck dissection and postoperative radiotherapy. The treatment of choice in patients with cervical CUP should be a surgical procedure including (radical) neck dissection and diagnostic bilateral tonsillectomy followed by postoperative radiation of the cervical lymph drainage. Bilateral tonsillectomy is especially important and is correlated with a significant improvement of the survival rate in CUP patients. Additional postoperative radiation of the entire pharyngeal and laryngeal mucosa should also be considered in order to treat a possible small primary tumor in this region.     

Positron emission tomography in the management of unknown primary head and neck carcinoma

OBJECTIVE: To assess the role of positron emission tomography (PET) in the management of unknown primary carcinoma of the head and neck region. DESIGN AND SETTING: Prospective case series at an academic medical center. PATIENTS: Twenty-six patients with an open excisional biopsy or a fine-needle aspiration biopsy finding that confirmed squamous cell carcinoma of the cervical lymph nodes and no visible primary tumor (as determined by results of a comprehensive physical examination and computed tomography and/or magnetic resonance imaging) underwent PET. The standard evaluation consisted of a comprehensive head and neck examination that included fiberoptic laryngoscopy/nasopharyngoscopy, computed tomography and/or magnetic resonance imaging, and PET followed by panendoscopy with selected biopsies and tonsillectomy. MAIN OUTCOME MEASURES: Sensitivity, specificity, and positive and negative predictive values of PET to detect an occult primary tumor. RESULTS: The PET detected 8 occult primary tumors in 26 patients (detection rate, 30.8%). Four occult primary tumors (2 at the base of the tongue and 2 in the tonsil) were detected during routine panendoscopy with negative PET findings. The sensitivity of PET was 66.0%, with a specificity of 92.9%. The positive predictive value was 88.8%, and the negative predictive value was 76.5%. CONCLUSIONS: Positron emission tomography can be a valuable tool to identify a subset of patients with an occult primary tumor in the head and neck region. In addition, it can be used to screen for primary tumors below the clavicle. Early identification of the primary tumor may allow for more accurate tumor staging and targeted radiotherapy to minimize adverse effects and complications. A normal PET finding, however, does not eliminate the need for a careful panendoscopy with directed biopsies and tonsillectomy.     

原发灶不明的颈部转移性鳞癌的临床特点

目的:通过对原发不明的颈部转移性鳞癌病例的临床分析,以了解其临床特点及颈部淋巴结的分布,为临床对此病的诊断、治疗和预后判断提供帮助。方法:回顾性分析了我院头颈外科１９８８~１９９８年间收治的原发不明的颈部转移性鳞癌３０例的临床特点,颈部淋巴结分布,治疗方法。结果:３０例原发不明的颈部转移性鳞癌病例的５年生存率为５６．１４%,１０年生存率４０．１９%。原发灶出现率为３０%,颈部淋巴结复发率为３３．３%,远处转移出现率２０%。淋巴结分群结果符合原发部位与颈部淋巴结之间的转移规律。预后分析结果:颈部淋巴结复发,出现远处转移和颈部治疗方法与预后相关。结论:颈部淋巴结的位置与原发肿瘤来源之间的转移规律有助于原发不明的颈部转移性鳞癌的正确诊断。在此基础上,应积极将可疑原发病灶包括在治疗中,并根据可疑原发肿瘤的类型选择手术或放射治疗。颈部转移灶的处理以颈部淋巴结清扫术加术后补充放疗的控制率为佳。     

Transoral robotic surgery for the management of head and neck squamous cell carcinoma of unknown primary

Conclusion: The addition of transoral robotic surgery (TORS) in the diagnostic management of patients classified with head and neck squamous cell carcinoma of unknown primary (SCCUP) is promising and appears to improve detection rates of the primary tumour. The approach presented in this first Scandinavian study could potentially minimize the radiation field to the pharyngeal axis in patients with identified primary tumours. Objectives: The aim of the study was to investigate whether bilateral lingual tonsillectomy performed with TORS is feasible, and whether it could improve the detection rates of primary tumours in patients diagnosed and classified as having SCCUP. Methods: The study was retrospective and included 13 patients with SCCUP who were referred to TORS between October 2013 and January 2015. All 13 patients had previously undergone a full investigation programme following the national guidelines including whole-body PET/CT, examination in general anaesthesia, including random biopsies of the base of the tongue and bilateral palatine tonsillectomy without identification of the primary tumour. Results: The primary tumour was identified by TORS in seven of the 13 patients (54%) at the lingual tonsils. Human papillomavirus DNA and p16 were positive in all identified primary tumour specimens and in the corresponding lymph node metastases.     

Metastatic basal cell carcinoma of the head and neck

Metastases are occasionally associated with cutaneous squamous cell carcinoma but only rarely with basal cell carcinoma. There are approximately 200 cases of metastases from basal cell carcinoma reported in the world literature. We describe 6 additional cases. All of our patients demonstrated recurrence at the primary site before they developed their metastases. Metastases presented in subcutaneous tissue, cervical lymph nodes, bone, and lung between 1.5 and 14 years after initial treatment of the primary lesion. The long interval seen in these patients between the initial treatment of the primary and the development of metastases underscores the need for long-term follow-up in what is often thought to be a nonaggressive, nonmetastasizing malignancy.     

Occult tonsillar carcinoma in the unknown primary

Objectives: Evaluate effectiveness of routine tonsillectomy in the assessment of patients with squamous cell carcinoma of the neck of unknown primary, and evaluate outcomes of this group compared with patients without a primary identified initially. Study Design: A retrospective review of the medical records of 37 patients presenting with an unknown primary tumor over a 10-year period. Methods: Charts were reviewed for age and sex of patients, methods of evaluation and diagnosis, sites of tissues obtained on biopsy, N stage of disease, and presence of extracapsular spread. Recurrence and survival data were collected over a mean follow-up period of 34 months. Results: All primary lesions discovered through pathologic evaluation arose from the tonsil (9/9), and all were detected in patients undergoing tonsillectomy in conjunction with direct laryngoscopy. None of the patients (0/9) with occult tonsillar carcinoma have had recurrence, in contrast to 60% (15/25) of remaining patients. Patients with tonsillar primary lesions demonstrated less extracapsular spread of disease (25%) than patients without tonsillar primaries (67%), despite similar N staging within the two groups. Conclusions: Occult tonsillar carcinoma accounts for the unknown primary more frequently than was previously recognized. Bilateral tonsillectomy is recommended to increase the detection yield and to capture the rare case of bilateral disease. A lower incidence of extracapsular spread and reduced recurrence rates in patients with unknown primary tumors presenting as occult tonsillar carcinoma may contribute to the improved prognosis observed in this group. Laryngoscope, 108:1605–1610, 1998     

Squamous cell carcinoma from an unknown head and neck primary site: a "selective treatment" approach

OBJECTIVE: To assess the efficacy of limiting treatment to the involved neck by way of neck dissection and adjuvant radiotherapy and reserving other therapies for salvage in the management of metastatic cervical squamous cell carcinoma from an unknown head and neck primary site. DESIGN: Retrospective study of patients whose clinicopathological data had been prospectively collected in a comprehensive head and neck database. SETTING: A tertiary referral university hospital. PATIENTS: The study population comprised 70 patients with metastatic cervical squamous cell carcinoma from an unknown head and neck primary site. INTERVENTIONS: Neck dissection alone in patients with pN1 disease confined to the lymph node. All remaining patients received neck dissection and adjuvant postoperative irradiation of the involved (dissected) neck. MAIN OUTCOME MEASURES: Incidence of primary, regional, and distant recurrence and disease-specific and overall survival. RESULTS: Nodal stage was pN1 in 5 patients (7%); pN2a in 13 (19%); pN2b in 30 (43%); pN2c in 4 (6%); and pN3 in 18 (26%). Neck dissection alone was performed in 10 patients (14%), while 60 patients (86%) underwent neck dissection and adjuvant irradiation. Median follow-up was 45 months. The primary tumor site emerged in 8 patients (11%). The 5-year control rates were 84% in the ipsilateral (dissected) neck and 93% in the contralateral (undissected) neck. The 5-year disease-specific and overall survival rates were 62% and 56%, respectively. Macroscopic extracapsular spread was the only statistically significant adverse prognostic factor (P < .001). CONCLUSIONS: The results of our selective treatment approach compare favorably with the results of other reported protocols using comprehensive irradiation or concurrent chemoradiation. However, patients with extracapsular spread and pN2 or pN3 disease were at high risk of treatment failure and may benefit from adjuvant chemoradiation. Although our protocol spares patients of potentially morbid therapies, salvage is rarely successful.     

Clinical analysis of cervical metastatis from an unknown primary carcinoma

From 1997 to 2004, 19 cases-18 men and 1 woman-with cervical lymph node metastasis from an unknown primary carcinoma were retrospectively investigated regarding the clinical observation and the treatment outcome. With respect to the histopathological types, 16 cases had squamous cell carcinoma, 2 cases had adenocarcinoma and 1 case had ductal carcinoma. As for the region of lymph node metastasis with maximum size, metastasis located in the upper deep cervical region arrounted for 84%. The presence of primary lesions was comfirmed in 11 cases (3 tonsil, 1 nasopharynx, 1 base of tongue, 2 hypopharynx, 1 esophagus, 1 larynx, 1 gallduct, 1 mammary gland) after the treatment of their metastatic leisions. Tonsillectomy and Blind biopsy were effective for 5 patients. Seventeen patients were treated with neck dissection. Eleven patients with neck dissection underwent radiotherapy. The overall 3-year survival rate as determined by the Kaplan-Meier method was 62%. The 3-year survival rate of the 17 cases whose metastatic leisions were treated with radical neck dissection was 66%. The 3-year survival rate of cases with known primary sites and cases with unknown primary sites after treatment were 55% and 83%, respectively. Radiotherapy with radical neck dissection was thought more effective than radical neck dissection for local and neck control.