Selective lymphadenectomy in patients with Merkel cell (cutaneous neuroendocrine) carcinoma

Background: Merkel cell carcinoma (MCC) is an aggressive cutaneous tumor with a propensity for local recurrence, regional and distant metastases. There are no well-defined prognostic factors that predict behavior of this tumor, nor are treatment guidelines well established. Methods: Staging of patients with a new diagnosis of MCC was attempted using selective lymphadenectomy concurrent with primary excision. Preoperative and intraoperative mapping, excision, and thorough histologic evaluation of the first lymph node draining the tumor primary site [sentinel node] was performed. Patients with tumor metastasis in the sentinel node underwent complete resection of the remainder of the lymph node basin. Results: Twelve patients underwent removal of 22 sentinel nodes. Two patients demonstrated metastatic disease in their sentinel lymph nodes, and complete dissection of the involved nodal basin revealed additional positive nodes. The node-negative patients received no further surgical therapy, with no evidence of recurrent local or regional disease at a maximum of 26 months follow-up (median 10.5 months). Conclusions: While the data are preliminary and initial follow-up is limited, early results suggest that sentinel lymph node mapping and excision may be a useful adjunct in the treatment of MCC. This technique may identify a population of patients who would benefit from further surgical lymph node excision.     

甲状腺乳头状癌前哨淋巴结活检与颈清扫术选择

目的 探讨用前哨淋巴结活检结果指导甲状腺乳头状癌颈侧淋巴结清扫的准确性及可行性.方法 前瞻性分析2007年8月至2010年9月51例临床淋巴结阴性甲状腺乳头状癌患者,术前1.5～8h在超声引导下向甲状腺原发肿瘤内注入99m锝-右旋糖酐,体积0.4 ml(74 MBq),术中在肿瘤周围注射1％亚甲蓝0.2～0.8 ml.采用联合法(核素法和染料法)定位前哨淋巴结,并行术中冰冻病理检查,与术后颈清扫标本常规病理进行对照.结果 51例患者中48例颈侧检出前哨淋巴结,检出率94.1％,其中核素法和染料法检出率分别为90.2％和66.7％.颈侧淋巴转移30例,其中3例前哨淋巴结中未发现转移癌灶.颈侧隐匿性淋巴转移率58.8％,Ⅱ区、Ⅲ区、Ⅳ区、Ⅴ区淋巴转移率分别为17.6％、52.9％、29.4％、0％.前哨淋巴结活检灵敏度、特异度、准确度、阳性及阴性预测值分别为90％、100％、94.1％、100％和87.5％.结论 前哨淋巴结活检安全、可行,对预测临床淋巴结阴性甲状腺乳头状癌颈侧淋巴转移和指导颈侧淋巴结清扫有重要的临床意义.     

Merkel cell carcinoma in the orbitopalpebral region

Trabecular carcinoma is a rare cutaneous neuroendocrine carcinoma that probably originates from the Merkel cells that are usually found in the basal layer of the epidermis. The treatment of Merkel cell carcinoma is controversial and there is no specific therapeutic protocol because of the small number of cases that have been published. The procedures used to treat Merkel cell carcinoma must be tailored to minimise morbidity while maximising survival. Because the condition is so rare and difficult to diagnose and treat, we report three cases of orbitopalpebral tumours that confirm the local and regional aggressiveness and the high metastatic potential of this tumour.     

Adjuvant locoregional radiotherapy as best practice in patients with Merkel cell carcinoma of the head and neck

BACKGROUND: Australians have the highest rate of skin cancer in the world. Merkel cell carcinoma (MCC) is the most aggressive skin cancer reported, with a high propensity for relapse. The purpose of this study was to report the patterns of recurrence after initial treatment, the outcomes, and any predictors for survival. METHODS: We identified 37 patients who were diagnosed with MCC of the head and neck between 1980 and 2002. In this retrospective analysis, multivariate analysis was performed by use of Cox regression analysis. Disease-free survival (DFS) and overall survival (OS) were calculated with Kaplan-Meier survival curves. RESULTS: The median age at diagnosis was 75 years (range, 46-89 years), with 24 men and 13 women. The median duration of follow-up was 26 months (range, 7-104 months). Twenty-nine patients (78%) initially were seen with a primary lesion, and eight (22%) had a primary lesion and clinical nodal disease. A total of 24 (65%) of 37 patients had a relapse, with regional relapse the most common site of the first relapse (12 of 37). The rates of local relapse were similar for patients undergoing local surgery (three of 17; 18%) or surgery and adjuvant radiotherapy (two of 19; 11%). Nodal relapse developed in seven (50%) of 14 patients not receiving regional treatment compared with six (26%) of 23 patients receiving regional treatment of some type. Patients treated with surgery and adjuvant radiotherapy experienced a significantly longer median DFS than did those undergoing surgery alone (23 months vs 6 months; p < .01). The 3-year OS and DFS rates for the entire study population were 66% and 25%, respectively. CONCLUSION: MCC is an aggressive skin cancer. There is a sufficient body of evidence, including this study, to consider the addition of adjuvant locoregional radiotherapy as best practice in markedly improving freedom from relapse.     

Merkel cell carcinoma of the head and neck

Merkel cell carcinomas are uncommon, but aggressive, cutaneous malignancies of neuroendocrine differentiation. To the pathologist, these lesions appear as sheets of undifferentiated tumor cells with little cytoplasm and dense nuclear chromatin. They are members of the group of "small round blue cell tumors," which includes small cell carcinomas of the lung, lymphomas, and neuroblastomas. Analogous to other skin malignancies, Merkel cell carcinomas frequently arise in the head and neck region and are commonly found in the elderly population. Merkel cell carcinomas have a high propensity for regional and distant metastases, and recurrences are frequently seen. Surgical excision is the recommended first-line treatment followed by adjuvant radiation therapy. Because of the high incidence of occult regional metastasis, patients with clinical and radioghaphically negative necks should undergo elective dissection, irradiation, or preferably sentinel lymph node biopsy.     

Sentinel lymph node biopsy performed under local anesthesia is feasible

BACKGROUND: A sentinel lymph node (SLN) biopsy in breast cancer patients, performed under local anesthesia (LA), could have advantages such as more efficient use of operating room time and pathologist time. It also provides a histologic diagnosis before definitive breast surgery is undertaken. The aim of this study was to assess feasibility by comparing the results of SLN procedures performed under LA versus general anesthesia (GA). METHODS: The SLN procedure was performed in 50 consecutive outpatients and 167 inpatients with clinical T1-2N0 breast cancer while they were under LA and GA, respectively. The SLN detection rate, a comparison of mapped and harvested SLNs, was compared for both groups. The duration of the SLN biopsies performed under LA was also measured. RESULTS: For both groups a median of 2 SLNs/patient were harvested. The detection rate was 1.00 for the LA group and 0.99 for the GA group. The learning curve for SLN procedures under LA showed a decrease in duration for the consecutive months (not significant). CONCLUSIONS: SLN biopsy can be safely and adequately performed with the patient under LA. It allows early diagnosis of the lymph node status, acquired on an outpatient basis, with minimal discomfort to the patient. The learning curve demonstrated that the LA procedure can quickly be mastered if the surgeon is experienced in performing SLN biopsies.     

Sentinel node biopsy for cutaneous melanoma in the head and neck

Background: Selective sentinel lymphadenectomy has gained widespread acceptance for staging of melanomas arising in the trunk and extremities, but the complex lymphatic drainage of the head and neck area has limited its application in this area.Methods: We performed a retrospective analysis of patients who underwent selective sentinel lymphadenectomy for cutaneous melanoma of the head and neck at the University of Alabama at Birmingham from 1997 through 2000, by using a standard technique of preoperative lymphoscintigram and biopsy guided with blue dye injection and a handheld gamma probe. Complete lymph node dissection was recommended only for tumor-positive sentinel lymph nodes (SLNs). Survival curves were constructed with the Kaplan-Meier method. Fishers exact test was used for comparisons. Significance was defined as P < .05.Results: Thirty-eight patients underwent selective sentinel lymphadenectomy with the standard technique during the study period. A majority (82%) of patients were men with a median age of 55 years. The most common site of the primary tumor was the face (44%), followed by the scalp (24%). Mean tumor thickness was 2.5 mm. The sentinel node was identified during surgery in 35 patients (92%). Before the use of the handheld gamma probe, the identification rate of the SLN was only 56%. A single SLN was identified in 53% of cases. The incidence of metastases in SLN was 11.4%. With a mean follow-up of 17 months, the actuarial 3-year overall survival was 92%. The accuracy of the selective sentinel lymphadenectomy in this series was 80%.Conclusions: Selective sentinel lymphadenectomy in the head and neck region is a technically demanding procedure, but the combined use of blue dye and gamma-probe radiolocalization can be a reliable method of staging regional lymph nodes and determining the need for elective lymphadenectomy.     

Sentinel node biopsy in breast cancer revisited

The axilla has long been a focus of clinicians' attention in the management of breast cancer. The approach to the axilla has undergone dramatic changes over the last century, from radical and extended radical excisions, through the introduction of sentinel node biopsy for node negative patients to the current situation where selective management of those with nodal involvement is being introduced.The introduction of lymphatic mapping and sentinel node biopsy in the 1990's has been key to the major changes that have occurred. In less than 20 years it has moved from a hypothesis to a situation where it is the default approach to almost all clinically node negative patients and is being considered in other situations where axillary clearance was previously considered standard. This article reviews the development and introduction of sentinel node biopsy, its current uncertainties and limitations, and possible future developments.     

Management of Merkel Cell Carcinoma: The Roles of Lymphoscintigraphy, Sentinel Lymph Node Biopsy and Adjuvant Radiotherapy

Background  Merkel cell carcinoma (MCC) is an uncommon, highly aggressive skin malignancy with a propensity to recur locally and regionally. However, its optimal treatment is uncertain. In this study, we aimed to assess the roles of lymphoscintigraphy and sentinel node (SN) biopsy, as well as radiotherapy, in the treatment of MCC. Patients and Methods  A retrospective analysis of 17 patients diagnosed with MCC (median age 74 years) over a 7-year period (median follow-up 16 months) was performed. Results  Of 11 patients. 3 had a positive SN biopsy and, despite adjuvant radiotherapy, 2 of these 3 developed regional lymph node (RLN) recurrence. Of the remaining 8 patients who had a negative SN biopsy, however, 5 also had RLN recurrences. There were 9 patients who received adjuvant radiotherapy (RT) to the primary site, with no in-field recurrences; and 8 who received RT to their RLN field, with only 2 developing regional nodal recurrences—both were SN biopsy positive. During the follow-up period, 2 patients died, only 1 due to MCC. Conclusion  The results suggest that SN status may not be an accurate predictor of loco-regional recurrence in MCC. However, they strongly reinforce previous reports that radiotherapy, both locally and to regional nodes, provides effective infield disease control.     

Sentinel node biopsy versus low axillary sampling in women with clinically node negative operable breast cancer

BackgroundSentinel node biopsy (SNB) was initially conceived as excision of the first station axillary lymph node(s) (LN) identified by radioactive and/or blue dye uptake. The definition was subsequently enlarged to also include palpable lymph nodes in the vicinity of sentinel node(s) (SN). We reasoned that the excision of this combination of nodes might be best achieved by sampling the lower axilla.MethodsEach patient underwent low axillary sampling (LAS) and identification of SN in the excised specimen followed by complete axillary lymph node dissection (ALND). LAS was defined as excision of all fibrofatty tissue overlying the second digitation of serratus anterior below the intercostobrachial nerve and was carried out following a pre-operative injection of radioactive colloid and an intra-operative injection of blue dye. Blue and/or hot nodes (B&/HN) in the dissected tissue and remaining axilla, along with any palpable nodes within the sampled tissue, were defined as SN. The primary endpoint of the study was to compare false negative rates (FNR) of SN with that of LAS in predicting axillary LN status (NCT00128362).FindingsThe study was performed between March 2004 and December 2011 in 478 women with clinically node negative axilla. On histopathological evaluation the median tumor size was 2.5 cm and axillary nodal metastases were found in 34.1% of patients. The FNR of SNB (12.7%, 95% CI 8.1–19.4) and LAS (10.5%, 95% CI 6.6–16.2) were not significantly different (p = 0.56). The FNR of B&/HN alone, without palpable nodes, (29.0%, 95% CI 22.5–36.6) was significantly inferior to those of SNB (p = 0.0007) and LAS (p = 0.0003).InterpretationLAS is as accurate as SNB in predicting axillary LN status in women with clinically node negative operable breast cancer. Confining SNB procedure to excision of B&/HN, significantly increases the risk of leaving behind metastatic lymph nodes in the axilla. LAS is an effective and low cost procedure that minimizes axillary surgery and can be implemented widely.Registry Name: Clinicaltrials.gov.Registration Number: NCT00128362.     

Sentinel node in head and neck cancer: use of size criterion to upstage the no neck in head and neck squamous cell carcinoma

BACKGROUND: Anatomical imaging tools demonstrate poor sensitivity in head and neck squamous cell carcinoma (HNSCC) patients with clinically node-negative necks (cN0). This study evaluates nodal size as a staging criterion for detection of cervical metastases, utilizing sentinel node biopsy (SNB) and additional pathology (step-serial sectioning, SSS; and immunohistochemistry, IHC). METHODS: Sixty-five patients with clinically N0 disease underwent SNB, with a mean of 2.4 nodes excised per patient. Nodes were fixed in formalin, bisected, and measured in 3 axes before hematoxylin-eosin staining. Negative nodes were subjected to SSS and IHC. SNB-positive patients underwent modified radical neck dissection. RESULTS: Maximum diameter was larger in levels II and III (13.1 and 13.2 mm) when compared with level I (10.5 mm; p = .004, p = .018), while minimum diameter was constant. Positive nodes were larger than negative nodes (p = .007), but nodes found positive by SSS/IHC were not significantly larger than negative nodes for either measurement (p = .433). Sensitivity and specificity were poor for all measurements. CONCLUSIONS: Nodal size is an inaccurate predictor of nodal metastases and should not be regarded as an accurate means of staging the clinically N0 neck.