Merkel cell cancer of the skin.

Merkel cell carcinoma (MCC) is a rare malignant cutaneous tumor of the elderly with rapidly growing skin nodules found predominantly on sun-exposed areas of the body. The vast majority of patients present with localized disease, while up to 30% have regional lymph node metastases. Despite local excision and the incidence of local recurrence, regional lymph node metastases and distant metastases is high and usually occurs within 2 years of primary diagnosis. The optimal treatment for patients with MCC remains unclear. The best outcome is achieved with multidisciplinary management including surgical excision of primary tumor with adequate margins and post-operative radiotherapy (RT) to control local and regional disease. Patients with regional nodal metastases should be treated with lymph node dissection plus RT. Adjuvant chemotherapy (CT) should be considered as part of the initial management. In case of metastatic disease CT based on regimens used for small-cell lung cancer is the standard treatment of care.     

Radiolocalization of the sentinel lymph node in Merkel cell carcinoma: A clinical analysis of seven cases

Merkel cell carcinoma (MCC) is a rare cutaneous skin lesion with a variable but often aggressive clinical course. Patient survival correlates with nodal status and the presence of distant metastases. The histologic status of the sentinel lymph node consistently correlates with the incidence of regional lymphatic metastases in other dermal malignancies. The technique of radiolocalization and surgical resection of the sentinel lymph node using an intraoperative gamma probe is used to guide clinical management in these patients. We report on seven cases of MCC managed utilizing this technique. Four patients had negative sentinel nodes and no other nodal disease at completion lymphadenectomy (n = 2) or clinical follow-up (n = 2) and currently remain disease free. Two patients had a positive sentinel node but no other positive lymph nodes at completion lymphadenectomy; one of them developed regional recurrence. One patient with a positive sentinel node and six additional positive nodes developed extensive nodal disease and systemic recurrence during radiotherapy and expired of MCC. Our results suggest that the sentinel node was identified and removed successfully using radiolocalization making this technique useful in the staging and therapy of patients with MCC. J. Surg. Oncol. 1998;67:251–254. © 1998 Wiley-Liss, Inc.     

The role of lymph node dissection in renal cell carcinoma: the pendulum swings back

The incidence of regional lymph node metastases in patients with renal cell carcinoma ranges from 13% to over 30%, and portends a poor prognosis in both locally advanced and metastatic settings. Patients with small, organ confined tumors are at low risk for regional lymph node metastases and lymph node dissection can be omitted in these patients. In contrast, patients with clinical evidence of regional lymph node metastases may derive therapeutic benefit from aggressive removal of all affected lymph nodes within the retroperitoneum. Patients with locally advanced primary tumors but no clinical evidence of lymphadenopathy can be selectively targeted for aggressive lymph node dissection as an adjunct to radical nephrectomy, based on their individual risk of harboring micrometastatic lymph node disease. Several predictive tools have been developed for prediction of occult retroperitoneal nodal metastases. Although early identification of micrometastatic nodal disease in this group of patients has not conclusively been shown to improve survival, accurate pathologic nodal staging allows for early implementation of adjuvant systemic therapies in these high-risk patients. No formal guidelines exist regarding the extent and boundaries of lymph node dissection at the time of radical nephrectomy; however, overwhelming evidence suggests that the staging accuracy of lymph node dissection can be markedly improved if extended template dissections, rather than limited node sampling, is implemented.     

Caught in the middle: case study of a brachial (sentry) lymph node recurrence after resection and locoregional breast radiotherapy

To reduce local recurrence, adjuvant locoregional radiotherapy is given routinely for post-mastectomy breast patients with 4 or more positive lymph nodes. Most institutions adopt a 3- or 4-field radiotherapy technique, in which the field and shielding placements are informed by bony anatomic landmarks viewed on digitally reconstructed radiographs.Here, we report on a 40-year-old woman who underwent a lumpectomy with axillary node dissection, followed by chemotherapy, completion mastectomy, and adjuvant locoregional radiotherapy (50 Gy in 25 fractions) for a multicentric pT1cN2aM0 invasive ductal carcinoma of the right breast. At 9 months after radiotherapy, she presented with a palpable brachial lymph node, a major draining node of the upper extremity, in the axilla, abutting the previous anterior supraclavicular and axillary radiation fields. This occurrence highlights the potential superolateral border of the level i axillary nodal chain and its relationship to the upper extremity lymphatics via the brachial ("sentry") node. Adapting the delineated nodal target volume in locoregional radiotherapy of the breast for disease with extensive nodal involvement or other high-risk pathologic indications may be warranted in certain situations. Careful imaging and an informed discussion with the patient is needed before deciding to treat the sentry node and including the acromial-clavicular joints, balanced with the potential increased risk of lymphedema.     

Squamous cell carcinoma of the extremities

Between January 1976 and January 1983, 37 cases of squamous cell carcinoma of the extremities have been treated at the King Faisal Specialist Hospital and Research Centre by the authors. Each case has arisen in an area of preexisting scar or sinus. Twenty-nine cases were treated by definitive amputation, with 2 local recurrences and 12 nodal metastases. Seven cases had local excision, with three local recurrences and two nodal metastases. Recurrence rate was highest in Grade II and Grade III lesions, and 11 of 15 cases with Grade II disease had metastases to the regional lymph nodes an average of 5 months after surgery. With Grade I disease patients, 4 of 15 had nodal metastases an average of 5 months after surgery. Prophylactic regional nodal irradiation or node dissection was performed in seven cases. None of these cases have shown nodal metastases at an average of 24 months following definitive surgery and radiation. Routine prophylactic regional node irradiation is recommended in all cases of peripheral squamous cell carcinoma.     

Predictors of survival and recurrence in the surgical treatment of merkel cell carcinoma of the extremities

PURPOSE: Merkel cell carcinoma (MCC) is a rare and aggressive malignancy that originates within the extremities in about 40% of cases. Treatment approaches to this tumor have not been standardized. The purpose of this study was to examine treatment approaches to extremity MCC and to determine predictors of recurrence and patient survival. METHODS: A retrospective review of 38 consecutive patients with surgically treated extremity MCC was performed. Patient demographics, histologic tumor stage and location and pre-existing malignancies were recorded. Patients were treated by wide-local excision (WLE) or Mohs' technique. Clinically negative regional lymph nodes were either observed (n = 16) or staged with elective lymphadenectomy or sentinel lymph node dissection (SLND) (n = 17), and clinically positive nodes underwent therapeutic node dissection (n = 5). Adjuvant radiotherapy (n = 21) and chemotherapy (n = 6) were noted, as well as time to tumor recurrence and overall patient survival. Predictors of recurrence and survival were analyzed using Kaplan-Meier method and log rank test. RESULTS: There was no difference in local recurrence rates when comparing Mohs' technique to WLE for the treatment of primary tumors. Although there was no survival advantage to lymph node dissection, lymph node status was effective in predicting the risk of regional recurrence. Radiation reduced the local recurrence rate (HR = 0.29, 95% CI [0.10, 0.85]), but did not lead to improved overall survival. CONCLUSION: Margin-negative excision of the MCC remains the mainstay of treatment. Surgical staging, preferably with SLND, identifies patients that may develop regional recurrence. This study further supports the important role of adjuvant radiation therapy in improving locoregional tumor control in the patients with MCC.     

Axilläre Lymphknotenmetastasen bei CUP

Women who present with axillary lymph node metastases and no other distant metastases and no evidence of a breast cancer primary represent a potentially curable subset of individuals with CUP. The standard approach is to perform an axillary lymph node dissection followed by adjuvant systemic treatment and radiotherapy according to published guidelines for lymph node positive primary breast cancer. Mastectomy is not mandatory. In most cases occult breast cancer is associated with good prognosis. Reported 5-year survival rates after treatment of an occult primary breast cancer with axillary metastases range from 60–90%.     

Apocrine gland carcinoma of the axilla: review of the literature and recommendations for treatment

Apocrine gland carcinoma is a rare form of sweat gland neoplasm with a distinctive cytologic appearance. Although the region of the axilla remains the most common site for these tumors, apocrine gland carcinoma of the anogenital region, eyelid, ear, chest, wrist, lip, foot, toe, and finger have been reported. Classically, these slow-growing lesions present as painless, colorless or reddish, firm or cystic nodules. More than half of the reported patients with apocrine carcinoma had lymph node metastases at the time of diagnosis. Wide local excision is standard therapy for these lesions. A therapeutic lymph node dissection is indicated for confirmed lymph node metastases and may have a role in the setting of a large or highly aggressive tumor with narrow surgical margins. Although apocrine gland carcinoma responds poorly to chemotherapy, adjuvant radiotherapy may be used in advanced local or regional disease. The authors describe a 69-year-old man with a large recurrent apocrine gland carcinoma of the axilla treated with en bloc excision with axillary dissection and offer a pertinent review of the English literature and recommendations for treatment.     

Radiotherapy for cutaneous malignant melanoma: rationale and indications

The use of radiation as adjuvant therapy for patients with cutaneous malignant melanoma has been hindered by the unsubstantiated belief that melanoma cells are radioresistant. An abundance of literature has now demonstrated that locoregional relapse of melanoma is common after surgery alone when certain clinicopathologic features are present. Features associated with a high risk of primary tumor recurrence include desmoplastic subtype, positive microscopic margins, recurrent disease, and thick primary lesions with ulceration or statellitosis. Features associated with a high risk of nodal relapse include extracapsular extension, involvement of four or more lymph nodes, lymph nodes measuring at least 3 cm, cervical lymph node location, and recurrent disease. Numerous studies support the efficacy of adjuvant irradiation in these clinical situations. Although data in the literature remain sparse, evidence also indicates that elective irradiation is effective in eradicating subclinical nodal metastases after removal of the primary melanoma. Consequently, there may be an opportunity to integrate radiotherapy into the multimodality treatment of patients at high risk of subclinical nodal disease, particularly those with an involved sentinel lymph node. Such patients are known to have a low rate of additional lymph node involvement, and thus in this group, a short course of radiotherapy may be an adequate substitute for regional lymph node dissection. This will be the topic of future research.     

原发灶不明的颈部淋巴结转移癌的治疗

目的 探讨原发灶不明的颈部转移癌的治疗方式。方法 分析81例病例资料，采用治疗方法为手术(S)、手术加放疗(S R)、手术加化疗(S C)、单纯放疗(R)、放化疗(R C)。结果 (S)11例，(S R)18例，(S C)5例，(R)19例，(R C)28例。手术包括单侧颈清30例，双侧颈清2例，局部切除2例。放射治疗剂量为40Gv～75Gv。全组5年总生存率为59．26％。中上颈部转移者5年生存率65．7％，其中转移性低分化癌的治疗方式为以放疗为主的综合治疗；转移性鳞癌则以手术为主；转移性腺癌以手术为主，其中的乳头状腺癌采用甲状腺癌联合根治术式，其5年生存率分别为62．5％、71．43％、62．5％。锁骨上区转移癌以化疗及放疗为主，5年生存率为28．57％。转移灶的部位、N分期、综合治疗及放疗范围影响5年生存率。结论 对原发灶不明的颈部转移癌的治疗，应根据淋巴结转移的部位和病理类型决定。     

Lymph nodal Merkel cell carcinoma: primary or metastatic disease? a clinical case

We report a case of Merkel cell carcinoma (MCC) presenting in the lymph nodes in the absence of a primary cutaneous site. The MCC was treated by palliative radiotherapy, which controlled the disease locally. Eight months after diagnosis a mass appeared on the ipsilateral knee; histopathological examination of this lesion confirmed the diagnosis of MCC. The patient died two months later due to the development of pulmonary metastases. Interestingly, the neoplastic tissue was confined to the regional lymph nodes for several months before the primary site appeared. Primary lymph nodal MCC is rare and the diagnosis is difficult. In our opinion the only way to make a diagnosis of primary lymph nodal MCC is by appropriate clinical follow-up.     

Controversies in the management of metastatic melanoma to regional lymphatic basins

The primary management of lymph nodes involved with metastatic melanoma is regional lymphadenectomy. Many controversies of regional lymph node dissection exist including extent and nature of the lymphadenectomy, treatment of lymphatic metastases in unusual locations and the role of adjuvant radiotherapy. Although radical neck dissection has been the gold standard for cervical disease, modified dissections do not seem to compromise regional control in appropriately selected patients. In the axilla, a Level I, II, and III dissection is most commonly performed. Combined superficial and deep groin dissection is justified for clinically palpable disease although management of patients with histologically positive yet clinically non-palpable disease is more controversial. Burden of disease, imaging, patient co-morbidity, and Cloquet nodal status must be considered. Many technical variations exist in an attempt to improve morbidity rates secondary to lymphadenectomy. Unfortunately, complication rates are difficult to compare secondary to variable study designs, definitions, and patient populations. Adjuvant radiation therapy appears warranted in patients with high risk of regional recurrence including bulky disease, extracapsular extension or cervical location.     

上皮样肉瘤14例临床分析

背景与目的:上皮样肉瘤是一种组织起源尚不清楚的罕见软组织肉瘤.其生物学行为独特,容易发生局部复发、淋巴结扩散和/或远处转移.本研究旨在探讨上皮样肉瘤(Epithelioid sarcoma)的临床特点、诊断、治疗和预后.方法:对我院1990年1月至2005年12月间收治的14例上皮样肉瘤临床资料进行回顾性分析,并结合随访资料进行生存分析.全组14例均接受手术治疗.首次手术均在外院进行.再次手术11例在我院进行(9例行扩大切除术,2例行截肢术;4例同时行区域淋巴结清扫术),3例仍在外院行局部切除术或扩大切除术.术后9例接受辅助性治疗,其中单纯放疗6例,放疗 化疗3例.结果:全组在本院病理科复检确诊为上皮样肉瘤.12例(85.7%)出现肿瘤局部复发.4例(28.6%)发现区域淋巴结转移,9例术后3年内死亡.全组总的1、2、5、10年生存率为71.43%、55.56%、27.78%和13.89%.结论:上皮样肉瘤恶性程度并不很高,但局部复发率高,容易发生淋巴结和/或远处转移,预后不佳.广泛性切除或根治性切除合并预防性区域淋巴结清扫术是治疗上皮样肉瘤的有效手段.     

Nodal basin recurrence following lymph node dissection for melanoma: implications for adjuvant radiotherapy

PURPOSE: To analyze patterns of failure in malignant melanoma patients with lymph node involvement who underwent complete lymph node dissection (LND) of the nodal basin. To determine prognostic factors predictive of local recurrence in the lymph node basin in order to select patients who may benefit from adjuvant radiotherapy. METHODS AND MATERIALS: A retrospective analysis of 338 patients undergoing complete LND for melanoma between 1970 and 1996 who had pathologically involved lymph nodes was performed. Mean follow-up from the time of LND was 54 months (range: 12-306 months). Lymph node basins dissected included the neck (56 patients), axilla (160 patients), and groin (122 patients). Two hundred fifty-three patients (75%) underwent therapeutic LND for clinically involved nodes, while 85 patients (25%) had elective dissections. Forty-four percent of patients received adjuvant systemic therapy. No patients received adjuvant radiotherapy to the lymph node basin. RESULTS: Overall and disease-specific survival for all patients at 10 years was 30% and 36%, respectively. Overall nodal basin recurrence was 30% at 10 years. Mean time to nodal basin recurrence was 12 months (range: 2-78 months). Site of nodal involvement was prognostic with 43%, 28%, and 23% nodal basin recurrence at 10 years with cervical, axillary, and inguinal involvement, respectively (p = 0.008). Extracapsular extension (ECE) led to a 10-year nodal basin failure rate of 63% vs. 23% without ECE (p < 0.0001). Patients undergoing a therapeutic dissection for clinically involved nodes had a 36% failure rate in the nodal basin at 10 years, compared to 16% for patients found to have involved nodes after elective dissection (p = 0.002). Lymph nodes larger than 6 cm led to a failure rate of 80% compared to 42% for nodes 3-6 cm and 24% for nodes less than 3 cm (p < 0.001). The number of lymph nodes involved also predicted for nodal basin failure with 25%, 46%, and 63% failure rates at 10 years for 1-3, 4-10, and > 10 nodes involved (p = 0.0001). There was no significant difference in nodal basin control in patients with synchronous or metachronous lymph node metastases, nor in patients receiving or not receiving adjuvant systemic therapy. Nodal basin failure was predictive of distant metastasis with 87% of patients with nodal basin recurrence developing distant disease compared to 54% of patients without nodal failure (p < 0.0001). On multivariate analysis, number of positive nodes and type of dissection (elective vs. therapeutic) were significant predictors of overall and disease-specific survival. Size of the largest lymph node was also predictive of disease-specific survival. Site of nodal involvement and ECE were significant predictors of nodal basin failure. CONCLUSIONS: Malignant melanoma patients with nodal involvement have a significant risk of nodal basin failure after LND if they have cervical involvement, ECE, >3 positive lymph nodes, clinically involved nodes, or any node larger than 3 cm. Patients with these risk factors should be considered for adjuvant radiotherapy to the lymph node basin to reduce the incidence of nodal basin recurrence. Patients with nodal basin failure are at higher risk of developing distant metastases.     

Merkel cell carcinoma arising in the head and neck: optimizing therapy

Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine dermal neoplasm. Because of the limited number of cases described in the literature (approximately 600 to date), statistically significant data regarding treatment are difficult to obtain. The majority of MCC cases affect the head and neck and are thought to be caused by the actinic damage associated with sun exposure. This study evaluates cases of head and neck MCC at Naval Medical Center San Diego (NMCSD) and compares the treatment regimens and outcomes from multiple institutions. This study is a retrospective outcomes analysis of all cases of head and neck MCC seen at NMCSD, between January 1, 1988 and June 30, 1998. The records of the NMCSD Tumor Registry were searched for patients with that diagnosis, and supplemental information was retrieved from the Radiation Oncology and Head & Neck Surgery Clinic charts. Eight of nine patients in this study were treated with either wide-local excision or Mohs microsurgery. The surgical margins were free of disease in all eight patients. One patient presented with distant metastatic disease, and two others were subsequently found to have nodal involvement. Subsequent therapy varied among the patients. Survey of the available literature revealed inconsistency in terms of which treatment regimens are optimal. Tumor resections are recommended by most groups to include a 2-cm to 3-cm tumor-free margin around the primary lesion when possible, but this is often difficult to achieve in the head and neck. Data, which do not reach statistical significance, suggest improved outcomes with tumor-free margins. Treatment of the regional draining lymph nodes is also recommended in most series. Prophylactic lymph node dissection or radiation therapy to the nodal chain may decrease local recurrence but does not consistently affect overall survival. Adjuvant chemotherapy is advocated by most groups in the treatment of metastatic disease because MCC is pathologically similar to small-cell lung carcinoma. However, no chemotherapy protocol has been shown to improve survival. Head and neck MCC is a rare and aggressive dermal tumor of neuroendocrine origin that requires multimodality therapy, including surgery, radiation therapy, and possibly adjuvant chemotherapy. Multiinstitutional studies are crucial to obtain sufficiently large populations to investigate and optimize therapy in this disease.     

Les tumeurs à cellules de Merkel,rôle de la radiothérapie. Analyse de la littérature

Merkel cell carcinoma (MCC) is a rare neuroendocrine carcinoma of the skin with features of epithelial differentiation. It occurs in older patients, appears on sun exposed areas and its incidence is increasing. The surgical excision with negative margins is the first treatment and adjuvant local irradiation now is well established but regional adjuvant (lymph nodes dissection or radiation therapy) remains discussed. MCC is chemosensitive but rarely chemocurable in patients with metastasis or locally advanced tumors. The most used therapy is platinum-based polychemotherapy.     

Major extremity amputation for nodal metastasis from squamous cell carcinoma

The regional lymph node basin is usually the first site of spread in cutaneous squamous cell carcinoma (SCC). Regional metastases are usually treated with comprehensive nodal dissection, sometimes followed by radiation and/or chemotherapy. Occasionally, when disease recurs after these conventional therapies, major extremity amputation may be the only way to render patients free of disease. We present three cases for which major extremity amputation was necessary. One patient underwent forequarter amputation for nodal metastasis, which had invaded the brachial plexus. Another patient underwent hip disarticulation for femoral bony invasion from inguinal nodal metastasis. The third patient underwent a hemipelvectomy for nodal metastasis, which had eroded the femoral artery and pelvic bone. These cases show that major extremity amputation can be both palliative and curative in patients with SCC.     

Recurrences in the soft tissues of the neck after surgery or radiotherapy plus surgery on regional lymph nodes in patients bearing carcinomas of the head and neck

A series of 45 recurrences in the soft tissues of the neck following lymph node dissection in 497 patients bearing carcinoma of the upper aerodigestive passages is reported. Only 22 cases that presented perilymph node metastases and/or in which there were reasons to indicate insufficient surgical radicality had been subjected to radiotherapy after surgical lymph node dissection; the other 23 cases had not been subjected to radiotherapy because the aforementioned premises had been lacking. All the recurrences therefore occurred in patients with clinically and histologically ascertained metastatic lymph nodes. The presence of perilymph node metastases and the judgment of surgical radicality was thus found insufficient criteria to plan future complementary postoperative radiotherapy. However, even in those cases in which postoperative radiotherapy was performed, there was a rather high incidence of recurrences, as high as 64.7% in patients with carcinoma of the tongue. Our data indicate the opportunity of a clinical trial with preoperative radiation therapy in patients with clinically evident lymph node metastases. Thirty-six of these recurrences were situated in the upper parts of the cervical region. The prognosis is very poor in such cases, so much so that only 2 of our series were disease free at 3 years after the treatment.     

Best practices in surgical and nonsurgical management of head and neck Merkel cell carcinoma: An update

Merkel cell carcinoma (MCC) is a rare, highly aggressive cutaneous neuroendocrine carcinoma. Controversy exists regarding optimal management of MCC as high-quality randomized studies and clinical trials are limited, and physicians are bound to interpret highly heterogeneous, retrospective literature in their clinical practice. Furthermore, the rising incidence and notably poor prognosis of MCC urges the establishment of best practices for optimal management of the primary tumor and its metastases. Herein, we summarized the relevant evidence and provided an algorithm for decision-making in MCC management based on the latest 2021 National Comprehensive Cancer Network guidelines. Additionally, we report current active MCC clinical trials in the United States. The initial management of MCC is dependent upon the pathology of the primary tumor and presence of metastatic disease. Patients with no clinical evidence of regional lymph node involvement generally require sentinel node biopsy (SLNB) while clinically node-positive patients should undergo fine needle aspiration (FNA) or core biopsy and full imaging workup. If SLNB or FNA/core biopsy are positive, a multidisciplinary team should be assembled to discuss if additional node dissection or adjuvant therapy is necessary. Wide local excision is optimal for primary tumor management and SLNB remains the preferred staging and predictive tool in MCC. The management of MCC has progressively improved in the last decade, particularly due to the establishment of immunotherapy as a new treatment option in advanced MCC. Ongoing trials and prospective studies are needed to further establish the best practices for MCC management.     

Axillary lymph node irradiation in breast cancer: state of the art

Place of axillary radiotherapy in the management of patients with breast cancer remains debated. While the prognostic value of axillary lymph node extension has been largely demonstrated, the benefit of axillary treatment is more uncertain. Large clinical trials having demonstrated the benefit of adjuvant radiotherapy in advanced breast cancer comprised large nodal irradiation, including axillary area. Analyzing the true benefit of axillary radiotherapy is rendered difficult by heterogeneity of series, particularly when focusing on the extent of lymph node dissection. Although adjuvant axillary radiotherapy is usually recommended in patients with insufficient lymph node dissection or with bulky axillary involvement, the prognosis in these patients remains poor by metastatic evolution and such strategy exposes to increased toxicity and functional sequels. Further assessments should better define the optimal indications and the true benefit of axillary radiotherapy.