An evaluation of the diagnostic methods in head and neck cancer of unknown primary site

Abstract

Background: Various detection methods to identify the primary in head and neck cancer of unknown primary (HN-CUP) require evaluation to improve and standardize management.

Objectives: To evaluate the use of different diagnostic methods, which aim at decreasing the incidence of HN-CUP.

Material and methods: We conducted a retrospective analysis of patients with HN-CUP at the Helsinki University Hospital during 1995–2011. We evaluated clinical assessment, definitive treatment, histopathology, and follow up. We analyzed the success in identifying the primary site to show any changes in diagnostic methods over time.

Results: Frequency of HN-CUP and success in identifying the primary site have remained constant despite the addition of PET-CT and determination of human papilloma virus (HPV) status in diagnostics. Among 133 patients, the diagnostic work up identified the primary site in 53% and the oropharynx predominated (69%). This left 85 patients with HN-CUP and 5-year overall and disease-free survival rates were 71 and 69%, respectively.

Conclusions: Panendoscopy including tonsillectomy should not be omitted in the work up.

Significance: We demonstrate a steady frequency of HN-CUP and constant success in identifying the primary site. Detection of a primary later in the follow up did not impact the survival.     

Role of the head and neck surgeon in sentinel lymph node biopsy for cutaneous head and neck melanoma

OBJECTIVE: To determine the reliability of sentinel lymph node biopsy (SLNB) in head and neck cutaneous melanomas to accurately stage nodal basins, describe techniques for safe SLNB in the neck and parotid regions, and discuss treatments. STUDY DESIGN: Retrospective chart review with follow-up mean of 11 months. METHODS: The charts of 80 patients treated for head and neck cutaneous malignancies from January 2001 through June 2003 were reviewed for presentation, treatment, and outcome. RESULTS: All patients received lymphoscintigraphy and SLNB for melanoma with Breslow thickness greater than 1 mm. Accurate preoperative lymphoscintigraphy and blue dye injection along with facial nerve monitoring when indicated correlated with safe SLNB. Eleven (14%) patients required completion surgery after positive SLNB and underwent evaluation for adjuvant therapies. There were three cases with complications: two postoperative hematomas and one seroma. CONCLUSIONS: Safe and reliable SLNB depends on the knowledge of the anatomy in the head and neck region, reliability of preoperative lymph node mapping with lymphoscintigraphy, and possible additions of blue dye injection and facial nerve monitoring. Complete surgical treatment of positive SLNB cases along with adjuvant therapies potentially improves control of these cutaneous malignancies with manageable morbidity.     

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.     

Sentinel lymph node biopsy staging for cutaneous malignant melanoma of the head and neck

Conclusion Sentinel lymph node biopsies (SLNBs) can be performed safely and with reasonable accuracy in HNM patients. The outcome provides important prognostic information concerning DFS and further treatment. However, one must recognize that SLNB is a multidisciplinary procedure with a learning curve for all. Objectives To evaluate efficacy of performing SLNBs in a series of consecutive patients with cutaneous head and neck melanoma (HNM)?≥?T1b from introduction of the procedure and 10 years onward. Method End-points comprised of SLNB outcome, disease-free survival (DFS), and overall survival (OS). Results SNs were harvested in 128 of 160 patients (median Breslow?=?2.0?mm, 29% ulcerated); success rate?=?80.0%, or 92.1% if excluding patients where SLNBs were omitted due to non-localization on pre-operative imaging or because of SN-location in the parotid basin. Ten patients (7.8%) had positive SLNBs and were offered early completion neck dissections. Of the 146 patients available for follow-up (median?=?27 months), 15.8% had recurrent disease. The risk of a regional nodal recurrence after a negative SLNB was 7.5%. SN-negative patients had improved DFS c.f. SN-positive patients (p?p?相似文献   

Use of low-dose technetium Tc 99m sulfur colloid to locate sentinel lymph nodes in melanoma of the head and neck: preliminary study

OBJECTIVES/HYPOTHESIS: Because sentinel lymph nodes are the first lymph nodes that drain a primary cancer site, results of sentinel lymph node (SLN) biopsy indicate status of the regional lymph nodes. Preoperative lymphoscintigraphy and intraoperative combined application of the handheld gamma probe and blue-dye technique (i.e., the "combined technique") was used previously to accurately identify the SLN, mostly in melanoma of the extremities and trunk and, sometimes, in melanoma of the head or neck, which is anatomically complex. Because of this complexity, melanoma in the head or neck is inherently problematic to treat: Localization of the SLN can be difficult or impossible because the primary cancer site can be near or overlapping the nodal basin. The objective of the present study was to determine the technical modifications and other considerations that can make SLN localization feasible in cases of melanoma occurring near or overlapping the nodal basin in the head or neck. STUDY DESIGN/METHODS: In a retrospective study of clinical records containing our database of melanoma diagnoses made between January 1996 and December 1999, we identified 27 patients diagnosed with stage I or II primary melanoma of the head or neck with clinically negative neck nodes who also had had preoperative lymphoscintigraphy. Of the 27 patients (17 male and 10 female patients; mean age, 54 y), 24 had SLN biopsy by intraoperative localization using both the handheld gamma probe and the blue-dye technique. RESULTS: Among the 27 patients who had SLN mapping, a median Breslow thickness of 1.8 mm was noted. Sentinel lymph node was noted at preoperative lymphoscintigraphy in 26 (96%) of the 27 patients. Activity of technetium Tc 99m (Tc-99m) sulfur colloid injected ranged from 10 to 1000 microCi (0.37 to 37 megabecquerel [MBq]). Intraoperative use of the combined technique for sentinel lymphadenectomy was successful in 92% of patients. Sentinel lymph nodes were identified in all 14 patients who received Tc-99m sulfur colloid at an activity level less than 60 microCi (2.2 MBq); mean activity level of injected TC-99m sulfur colloid was 28 microCi (1.04 MBq). Sentinel lymph nodes were identified in 8 (80%) of 10 patients who received Tc-99m sulfur colloid at an activity level greater than 100 microCi (3.7 MBq); mean activity of injected Tc-99m sulfur colloid in these patients was 482 microCi (17.8 MBq). A mean number of 1.4 sentinel lymph nodes per patient was identified at preoperative lymphoscintigraphy, and a mean number of 3 sentinel lymph nodes per patient was identified intraoperatively using the combined technique. Tumor recurrence was seen in 2 (10%) of the 19 patients who had cancer-free SLN at mean follow-up of 18 months (range, 1 to 47 mo). Sentinel lymphadenectomy of the parotid region did not injure the facial nerve in any patients. CONCLUSIONS: For patients with primary melanoma that is near or overlaps the nodal basin in the head or neck, SLN biopsy can be accurately performed using Tc-99m sulfur colloid at low activity levels (10 microCi to 60 microCi [0.37 to 2.2 MBq]. However, background radiation from the primary injection site can incorporate the SLN, making localization at preoperative lymphoscintigraphy difficult if not impossible; therefore, the high doses commonly used for melanoma of the extremities and trunk (500 to 2000 microCi [18.5 to 74 MBq]) should not be used for melanoma of the head or neck if the primary site is near or overlaps the nodal basin. In addition, absorption of Tc-99m sulfur colloid by salivary glands increases background radiation in the nodal basin; therefore, use of the handheld gamma probe for intraoperative localization of SLN can be problematic in regions where lymph nodes are adjacent to or within the substance of the salivary gland (i.e., the submandibular and parotid glands).     

Diagnostic work-up and outcome of cervical metastases from an unknown primary

Conclusions. An intensive diagnostic work-up including ¹⁸F-fluorodeoxyglucose positron emission tomography (FDG-PET) detects many unknown primary tumours, leads to a low emergence rate of primary tumours, and selects carcinoma of unknown primary with much more favourable results after neck dissection and postoperative radiotherapy. Objective. To investigate the optimal diagnostic approach and best treatment modality for rare head and neck cancer of unknown primary. Patients and methods. In a retrospective study, 69 patients admitted from 1987 to 2002 with cervical lymph node metastases without apparent primary were reviewed. Test characteristics of all diagnostic procedures were calculated. Disease-free and overall survival rates were calculated. Major prognostic factors were analysed univariately. Results. At the primary site FDG-PET showed the best sensitivity with 69% and the highest negative predictive value with 87%. Computed tomography and magnetic resonance imaging had a better specificity with 87% and 95%, respectively. The primary tumour was detected in 23 cases (33%). Frequent primary tumour origin was the palatine tonsil (n=8, 35%), base of the tongue (n=6, 26%) and lung (n=4, 17%). All patients with unknown primary were treated by neck dissection. Adjuvant radiotherapy was performed in 26 patients (57%), concurrent radiochemotherapy was performed in 12 patients (26%). The primary emergence rate was 7%. The 5-year overall survival rate was inferior in patients with detected primary in comparison with patients with unknown primary (22% versus 52%). Significant prognostic factors in case of unknown primary were M stage, smoking, alcohol consumption and tonsillectomy. Radiotherapy but not chemotherapy with carboplatin influenced the overall survival.     

Prognostic factors of neck node metastasis

A retrospective clinico-pathological study has been carried out in a series of 405 patients with squamous cell carcinoma of the head and neck who underwent a total of 484 radical neck dissections. The recurrence rate in the neck in 327 patients who had histological positive nodes was 21.1%, Recurrence in the neck after a standard radical neck dissection almost invariably proved fatal. A statistical analysis has been carried out to evaluate the clinical and pathological factors which are of importance in regards to recurrence in the neck. Histological factors such as extra-nodal spread and the number of histological positive nodes have been shown to be of much more prognostic importance than clinical parameters. When corrections are made for interdependencies between variables, histological extra-nodal spread proved to be the most important single prognostic factor (P < 10^?7).     

Elective, therapeutic, and delayed lymph node dissection for malignant melanoma of the head and neck: analysis of 1444 patients from 1970 to 1998

OBJECTIVE: The purpose of this article is to evaluate the effects on survival, disease-free interval, and recurrence patterns for patients undergoing elective, therapeutic, and delayed lymph node dissection for malignant melanoma of the head and neck. STUDY DESIGN AND METHODS: A retrospective computer-aided analysis was performed comparing 1444 patients treated from 1970 to 1998 at Duke University Medical Center. A total of 446 of the 1444 (32%) of patients with head and neck melanoma underwent some form of lymph node dissection. Survival, disease-free interval, and recurrence rates for patients having 1) no initial lymph node dissection (no LND), 2) elective lymph node dissection (ELND) within 2 months of date of diagnosis, 3) therapeutic lymph node dissection (TLND) for metastatic regional disease at diagnosis, or 4) delayed lymph node dissection (DLND) for patients developing regional lymph node metastasis later than 3 months from the date of diagnosis were compared. RESULTS: A total of 246 patients undergoing ELND demonstrated 11% with occult disease. DLND for regional lymph node recurrence was reported at a median time interval of 1.2 years from diagnosis. Multivariate analysis indicated a significant improvement in survival for DLND when compared with patients undergoing ELND plus sign in circle or TLND (P =.01). Distant metastasis was the site of first recurrence in 12% of patients undergoing no initial LND. Five-year survival after DLND and TLND was 56% and 36%, respectively. CONCLUSION: Patients undergoing DLND had an overall better survival than patients undergoing TLND or ELND with positive nodes. The progression of metastatic disease following regional node disease occurred in 35% to 45% of cases, underscoring the need for effective adjunctive therapy.     

A review of clinical and histological parameters associated with contralateral neck metastases in oral squamous cell carcinoma

Oral squamous cell carcinoma(OSCC)bas a high incidence of cervical micrometastases and sometimes metastasizes contralaterally because of the rich lymphatic intercommunications relative to submucosal plexus of oral cavity that freely communicate across the midline,and it can facilitate the spread of neoplastic cells to any area of the neck consequently.Clinical and histopathologic factors continue to provide predictive information to contralateral neck metastases(CLNM)in OSCC,which determine prophylactic and adjuvant treatments for an individual patient.This review describes the predictive value of clinical-histopathologic factors,which relate to primary tumor and cervical lymph nodes,and surgical dissection and adjuvant treatments.In addition,the indications for elective contralateral neck dissection and adjuvant radiotherapy(aRT)and strategies for follow-up are offered,which is strongly focused by clinicians to prevent later CLNM and poor prognosis subsequently.     

Sentinel lymph node biopsy in head and neck squamous cell carcinoma

OBJECTIVES/HYPOTHESIS: Sentinel lymph node biopsy is a minimally invasive method to stage the regional lymphatics that has revolutionized the management of patients with intermediate-thickness cutaneous melanoma. Head and neck surgeons have been encouraged by the accuracy of sentinel lymph node biopsy in cutaneous melanoma and have applied the technique to patients with head and neck squamous cell carcinoma (HNSCC). The objectives of the study were 1) to study the feasibility and accuracy of sentinel lymph node biopsy as a method to stage the regional lymphatics in HNSCC and 2) to determine whether there are qualitative differences between the cutaneous and mucosal lymphatics that would affect the technique used in HNSCC. STUDY DESIGN: Two methods of investigation were employed: a prospective laboratory study using a feline model for sentinel lymph node biopsy and a retrospective review of patients who received lymphoscintigraphy before neck dissection and intraoperative identification of the sentinel lymph node. METHODS: Lymphoscintigraphy and a gamma probe were used in four felines to study the kinetics of technetium-labeled sulfa colloid (Tc-SC) in the mucosal lymphatics. In the second part of the feline study, eight subjects were studied intraoperatively. Tc-SC and isosulfan blue dye were used to study the injection technique for the mucosal lymphatics and to determine the time course of the dye and Tc-SC to the sentinel lymph node. In Part II of the present study, a retrospective review of 33 patients with HNSCC was conducted. Twenty patients (stage N0) whose treatment included elective neck dissection were studied with preoperative lymphoscintigraphy and underwent intraoperative identification of the sentinel lymph node to determine the accuracy and feasibility of sentinel lymph node biopsy. Eight patients with palpable neck disease and five patients with recurrent or second primary disease whose previous treatment included neck dissection were also studied with lymphoscintigraphy before neck dissection. RESULTS: In the feline study, both Tc-SC and isosulfan blue dye traversed the lymphatics rapidly, appearing in the sentinel lymph node in less than 5 minutes. Modification of the injection technique used for cutaneous melanoma was required to depict the sentinel lymph node of the base of tongue. In the human study, the sentinel lymph node was accurately identified in 19 of 20 (95%) N0 patients. On average, 2.9 sentinel lymph nodes (range, 1-5) were identified in 2.2 (range, 1-4) levels of the neck. Sentinel lymph nodes were bilateral in 4 of 19 patients. When the sentinel lymph node was identified, it accurately predicted the pathological nodal status of the regional lymphatics. Three of 20 patients had cervical metastases, and the sentinel lymph node was identified in 2 of 3 patients with pathologic nodes (pN+). Focal areas of radiotracer uptake were identified in seven of eight patients with palpable disease. These areas corresponded to the level with palpable disease in four patients. The lymphatics delineated by lymphoscintigraphy in the five patients with previous neck dissection were outside the levels that had been dissected. Lymphoscintigraphy depicted collateral patterns of lymphatic drainage. CONCLUSIONS: Sentinel lymph node biopsy is technically feasible and is a promising, minimally invasive method for staging the regional lymphatics in patients with stage N0 HNSCC. Lymphoscintigraphy alone may determine the levels that require treatment in patients with disrupted or previously operated cervical lymphatics.     

Lymph node metastases from cutaneous squamous cell carcinoma of the head and neck

OBJECTIVE/HYPOTHESIS: Cutaneous squamous cell carcinoma (CSCC) has been reported to metastasize to parotid and cervical lymph nodes. Few prospective investigations of associated clinical and histopathologic findings and their effect on patient outcomes exist. We seek to identify risk factors for nodal metastases in CSCC and determine the impact of lymphatic spread on survival and recurrence. STUDY DESIGN: Subset analysis of a prospective, longitudinal database of patients with CSCC at a comprehensive cancer center. METHODS: Eligible patients with nonmelanoma skin cancer were consecutively enrolled in a prospective database from July 1996 through June 2001; this cohort was then followed to the key endpoints of recurrence and mortality. RESULTS: Two hundred ten patients were enrolled, and 193 patients with CSCC of the head and neck are included in this analysis. The incidence of nodal metastases in this population was 20.7% at study entry. Median follow-up was 20 months in patients with lymph node metastases and 24 months in patients without metastases. Nodal metastases were significantly associated with recurrent lesions (P = .002) and the following histopathologic features: lymphovascular invasion (P < .0001), inflammation (P = .010), poorly differentiated histology (P = .001), invasion into the subcutaneous tissues (P = .0001), perineural invasion (P = .005), and larger size (P = .0007). Metastases to the cervical nodes were not clinically apparent in 42% of patients with parotid metastases. Combination surgery and radiation therapy resulted in regional control rates of 95%, although local recurrence and distant metastases, along with second primary tumors, were the most frequent recurrent events. Kaplan-Meier survival analysis demonstrates a decrease in overall survival (P = .005), disease-free survival (P = .015), disease-specific survival (P = 0002), and time to recurrence (P = .012) in patients with nodal metastases compared with controls. CONCLUSIONS: Lymph node metastases from CSCC are common in our population and are associated with diminished survival. The presence of nodal spread occurs with other adverse histopathologic findings, and we recommend surgery and postoperative radiation therapy to control regional disease in the presence of nodal metastases and perineural invasion. New approaches in early identification of nodal metastases, treatment, and prevention of local recurrences and second primary malignancies are warranted.     

Lymph node metastases in the neck of unknown primary tumor

BACKGROUND: Cervical lymph nodes represent the most frequent manifestation of lymph node metastases of unknown primary. Nearly 3% of all malignant ENT-tumors are cervical lymph nodes metastases of unknown primary. This disease is a challenge for clinical working physician in diagnosis and therapy. MATERIAL AND METHOD: In a retrospective study we investigated 99 patients with the diagnosis cervical lymph node metastases of unknown primary, which were treated and observed in our department between 1975 and 1995. Within this group we observed the course of 83 patients completely. RESULTS AND CONCLUSIONS: The tumor-dependent 5 year-survival-rate was 11%. This is very low, but similar to the literature. 40% of patients, that were operated on neck dissection with or without postoperative irradiation survived tumor-dependent 5 years. In 42 cases we could find a primary tumor. 14 of these primaries were located in the upper aero-digestive-tract, 28 in other regions of the body. The identification of the primary did not improve the prognosis of the patients. A good prognosis was associated with further occult primary, location of the lymph nodes in the upper or middle level of the neck or parotid region and a histology of squamous cell or undifferentiated carcinoma. Signs of poor prognosis were metastasis in the supraclavicular region, of adenocarcinoma and inoperability of the lymph node. The combination therapy of neck dissection and irradiation proved to be best. The extended field radiation of the complete upper aero-digestive-tract did not cause a improvement of tumor-dependent 5-year-survival. We discovered a primary in 5 of 27 patients in this group within the irradiated area. In conclusion extended field radiation must be discussed critically for patients with lymph node metastasis of unknown primary.     

原发于头颈以外恶性肿瘤的颈淋巴转移临床分析

目的探讨原发于头颈以外的恶性肿瘤的颈淋巴转移规律，以期对此类疾病进一步认识，为诊断提供依据。方法回顾性分析自1989年1月至2004年6月在北京协和医院住院治疗的466例发生颈淋巴转移的恶性肿瘤患者之中的77例原发灶位于头颈以外的病例，均经病理证实为恶性肿瘤颈淋巴转移。分析其发病特点，并按照颈淋巴结LEVEL分区探讨颈淋巴转移区域的特点。结果77例原发于头颈以外的恶性肿瘤病例，原发部位包括肺、胃、食管、乳腺、结肠、纵隔、卵巢、子宫、胰腺、肝脏、肠系膜、肾上腺、直肠。81．8％（63／77）的患者发生LEVELⅤ区颈淋巴转移，其中50例为左侧LEVELⅤ区转移；11．7％（9／77）发生LEVELⅣ区转移；5．2％（4／77）发生LEVELⅢ区转移；1．3％（1／77）发生LEVELⅠ区转移。原发灶位于头颈部以外的病例占各区域全部病例的比例分别为LEVELⅠ区2．1％，LEVELⅢ区3．7％，LEVELⅣ区14．3％，LEVELⅤ区70．8％。发生颈淋巴转移的头颈外恶性肿瘤中，低分化腺癌占51．9％，中分化腺癌占15．6％，低分化鳞癌占11．7％，中分化鳞癌占10．4％，其他组织学类型占10．4％。结论头颈部以外的多个器官的恶性肿瘤均可见颈淋巴转移，其中以肺癌最为常见，胃、食管、乳腺也是常见的原发灶。头颈部以外的恶性肿瘤发生颈淋巴转移的区域集中在LEVELⅤ区，尤其是左侧LEVELⅤ区。且发生于LEVELⅤ区的肿瘤转移病例，原发肿瘤位于头颈部以外的情况多于头颈部肿瘤。发生颈淋巴转移的头颈外恶性肿瘤，分化程度以中．低分化为主。     

Intraparotid sentinel lymph node biopsy for head and neck melanoma

OBJECTIVE: The objective of this retrospective clinical review was to assess the safety and accuracy of intraparotid sentinel node biopsy in patients with melanoma. SETTING: This study was conducted at a tertiary referral center. PATIENTS: Twenty-eight patients with cutaneous melanoma of the head and neck undergoing sentinel lymph node (SLN) biopsy in which the radionuclide localized to the parotid gland on preoperative lymphoscintigraphy were studied. METHODS: All patients underwent wide local excision of the tumor and intraparotid sentinel node biopsy using intraoperative gamma probe localization. RESULTS: There were 25 men and 3 women ranging in age from 34 to 81 years. The primary site was on the auricle in 14 patients: temple, 4; forehead, 5; cheek, 3; and on the neck in 2 patients, respectively. The mean Breslow thickness was 2.3 mm (range, 0.9-7.0 mm). In 27 of 28 patients, an intraparotid SLN was identified. In one patient, final pathology did not reveal lymphoid tissue despite a high count in the parotid tissue excised. Median number of SLN per patient was two. Six patients had microscopic metastases in the SLN. In two of these patients, additional microscopic lymph node metastases were found in the neck after subsequent formal lymphadenectomy. The pathologic staging for the group (n = 14) was: stage 1B, 4; 2A, 4; stage 2B, 3; and stage 3B, 3 patients, respectively. All patients are alive and without evidence of disease (mean follow up, 31 months). There were no surgical complications, specifically no patient experienced temporary or permanent facial paralysis. CONCLUSION: Intraparotid SLN biopsy for staging cutaneous head and neck melanoma is a reliable, accurate, and safe procedure.