Primary neuroendocrine carcinoma of the skin (Merkel cell tumor)]

Primary neuroendocrine carcinoma of the skin (Merkel cell tumor), a rare malignancy originating from the skin, has only been established in the recent years. It has a main predilection on the skin in the head and neck region with an obvious tendency of local recurrence and early metastasis. Histopathologically, it resembles the neuroendocrine carcinoma from other sites of the body in morphology, immunohistochemistry and ultrastructure. Diagnosis of this tumor is quite difficult. Based upon two of our cases as verified by electron microscopy and/or immunohistochemistry, the clinical and pathological features of this tumor are described and the literature reviewed.     

Primary neuroendocrine carcinoma of the skin (Merkel's cell carcinoma)

Primary neuroendocrine carcinoma of the skin (Merkel's cell carcinoma) is a rare tumor. Until recently 86 patients with this tumor have been described. Two cases of this tumor are presented. This neoplasm has a high propensity for lymphatic as well as hematogenous metastases. It presents as a dermal or subcutaneous nodule. Awareness of this condition may lead to earlier diagnosis and improved survival.     

Merkle cell carcinoma report of a case and possible role for adjuvant radiotherapy

A case of neuroendocrine (Merkle cell) carcinoma of the skin is described. This uncommon tumor occurred in a 76-year-old female and presented as a small exophytic nodule on the right anterior chest wall. Following primary excision, it was thought to be a basal cell carcinoma. The diagnosis of Merkle cell carcinoma was established only after the tumor had recurred locally and involved ipsilateral axillary lymph nodes. Although local control was achieved with surgery and radiotherapy, the patient died of probable hepatic metastases 18 months after presentation. The Merkle cell tumor is an undifferentiated small cell carcinoma originating in the skin and has distinct ultrastructural characteristics that help to differentiate it from other small cell tumors. The clinicopathologic characteristics of these potentially aggressive neoplasms are reviewed, and treatment is briefly discussed.     

A Case of High-Grade Neuroendocrine Carcinoma That Improved with Bevacizumab plus Modified FOLFOX6 as the Fourth-Line Chemotherapy

High-grade neuroendocrine carcinoma differs from usual neuroendocrine carcinoma, and its prognosis is dismal. In this case report, a case of high-grade neuroendocrine carcinoma that improved with bevacizumab plus modified FOLFOX6 as the fourth-line chemotherapy is presented. A 29-year-old male with a huge liver tumor was diagnosed with high-grade neuroendocrine carcinoma originating from the liver. Multiple liver and bone metastases were found one month after surgery. He was treated with three chemotherapy regimens used for the management of small-cell lung cancer with extensive disease. However, none of them could be maintained because of tumor progression. He was then treated with bevacizumab plus modified FOLFOX6 as the fourth-line regimen. Dramatic tumor shrinkage was obtained, and a partial response was achieved. This case suggests that high-grade neuroendocrine carcinoma can be treated with bevacizumab in combination with cytotoxic chemotherapy.     

结直肠神经内分泌肿瘤的研究进展

结直肠神经内分泌肿瘤来源于结直肠神经内分泌细胞,发病率较低,但近年有上升趋势.WHO病理学将结直肠神经内分泌肿瘤分为神经内分泌瘤、神经内分泌癌、混合型腺-神经内分泌癌和增生性及肿瘤前病变.结直肠神经内分泌肿瘤细胞具有激素合成及分泌功能,但不一定都出现相应的临床症状.不同分类、分期的结直肠神经内分泌肿瘤的诊断及治疗方法也...     

Clinical characterization of pulmonary large cell neuroendocrine carcinoma and large cell carcinoma with neuroendocrine morphology

BACKGROUND: Large cell carcinoma has been classified as four potential types based on its neuroendocrine morphology and evidence of neuroendocrine differentiation discernible by immunohistochemistry or electron microscopy. However, the clinical relation among these four categories has not been clearly defined. In 1999, the World Health Organization (WHO) categorized large cell neuroendocrine carcinoma as a variant of large cell carcinoma. MATERIAL AND METHODS The authors analyzed 119 cases of large cell carcinoma from a total of 2070 primary lung carcinoma cases resected surgically between 1969-1999. Using light microscopy, electron microscopy, and immunohistochemical staining, the authors reclassified these cases into large cell neuroendocrine carcinoma (LCNEC), large cell carcinoma with neuroendocrine differentiation (LCCND), large cell carcinoma with neuroendocrine morphology (LCCNM), and classic large cell carcinoma (CLCC). RESULTS: In multivariate analyses, the authors found that large cell carcinoma with neuroendocrine features, which combined LCNEC, LCCND, and LCCNM, impacted both the overall survival and disease-free survival of patients. The clinical behavior of LCCNM was similar to that of LCNEC. CONCLUSIONS: Large cell carcinomas with neuroendocrine features appear to be more clinically aggressive than CLCCs. The authors' findings suggest that the histologic identification of neuroendocrine features in tumor tissue from patients diagnosed with large cell carcinoma of the lung may have clinical relevance.     

Merkel细胞瘤一例报告并文献复习

 通过一例经手术, 病理证实的Merkel细胞瘤, 复习了相关文献, 对该病的临床特征, 诊断, 治疗原则, 预后因素及分子生物学研究进展进行了讨论。 Merkel细胞瘤是起源于浅表皮肤Merkel细胞的恶性肿瘤, 属于神经内分泌瘤。 肿瘤常见于头颈部及四肢, 易局部复发并转移。 主要靠病理诊断, 易与淋巴瘤混淆。 发病早期即主张行胸腹部CT检查以确定分期。 治疗原则倾向于先作肿物广泛切除, 淋巴结清扫, 尔后放疗。 化疗的作用尚不能肯定。 局部复发及有远处转移者预后差。 本病发生与BC1-2基因及FHIT基因有关, 与P53基因无关。     

Bilateral renal metastases in a case of Merkel cell carcinoma

Merkel cell carcinoma is a primary neuroendocrine carcinoma of the skin. It is a highly aggressive tumor which commonly metastasizes to lymph nodes, liver, lung and bone. The diagnosis is based on histology and immunohistochemistry. Renal metastasis, with sparing of other common sites of hematogenous spread (lung and liver), is a unique feature of this case.     

Primary neuroendocrine carcinoma of the breast: a case report

Primary neuroendocrine carcinoma of the breast is an extremely rare tumor. We present our experience of primary neuroendocrine carcinoma of the breast in a 76-year-old woman. Surgical biopsies from breast and axillary lymphadenopathy showed a neuroendocrine carcinoma. Immunohistochemical staining of tumor cells with GCDFP15, NSE and chromogranin were positive. Computed tomography scans of the chest and abdomen showed no lesion for metastasis or another primary origin. Adjuvant hormone therapy was given, since the tumor was immunohistochemically receptor positive.     

Neuron-specific enolase as a new tumor marker

Enolase is a glycolytic enzyme widely distributed in each mammalian tissue and consists of three distinct subunits alpha, beta, and gamma. In the brain enolase exhibits three dimetric isozymic forms: alpha alpha, alpha gamma and gamma gamma. The gamma protein subunit has recently been found to be identical with the nervous system-specific and species-nonspecific protein, 14-3-2; therefore, alpha gamma and gamma gamma types of enolase were characterized as neuron-specific enolase (NSE). NSE has been also detected in the pituitary gland, thyroid gland, adrenal medulla and pancreas, all of which contain neuroendocrine cells. Recently NSE was observed by immunostaining or radioimmunoassay in neuroendocrine tumor such as glucagonomas, insulinomas, gut carcinoids, medullary thyroid carcinomas or neuroblastomas. Furthermore, small cell carcinoma of the lung which has been known to frequently exhibit neuroendocrine properties was found to produce NSE. In this paper NSE as a tumor marker in various cancers was evaluated by immunostaining or enzyme immunoassay which was developed by a co-worker Kato. The data revealed that serum NSE was clinically useful as a tumor marker, especially a monitoring marker of disease extent. NSE productions were also observed in adenocarcinoma of the colon or the lung and large cell carcinoma of the lung as well as small cell carcinoma of the lung and the esophagus, all of which were considered to share the biochemical features of neuroendocrine tumor. The evidence challenges a speculation that small cell carcinoma of the lung has an origin separated from the other histological types of lung carcinoma. In this meaning NSE is an important tumor marker for both clinical medicine and basic research.     

Large cell neuroendocrine carcinoma of the lung: a comparison with large cell carcinoma with neuroendocrine morphology and small cell carcinoma

Large cell neuroendocrine carcinoma (LCNEC) of the lung is a malignant neuroendocrine tumor clinicopathologically similar to and falling in-between atypical carcinoid tumor and small cell lung carcinoma (SCLC). The diagnosis of LCNEC is based mainly on a characteristic neuroendocrine morphology and biological neuroendocrine differentiation. In order to know the discrepancy between morphological and biological neuroendocrine differentiation, LCNEC was immunohistochemically and molecular biologically compared with large cell carcinoma with neuroendocrine morphology (LCCNM), which lacked only biological neuroendocrine differentiation among the criteria of LCNEC. Immunohistochemically, disruption of the RB pathway, namely a lack of RB expression and simultaneous overexpression of p16 protein, was characteristic of LCNEC, but not LCCNM. In G2/M cell cycle regulation, 14-3-3 sigma expression was markedly reduced in LCNEC. Moreover, the antibody 34 beta E12 recognizing a set of large-sized keratin gave a different staining pattern between LCNEC and LCCNM. The immunohistochemical data suggested that LCNEC has a similar biological marker profile to SCLC and different from LCCNM. However, a loss of heterozygosity (LOH) analysis using microsatellite markers showed a high frequency of LOH at 3p in both LCNEC and LCCNM as well as in SCLC. Morphological neuroendocrine differentiation might not be identical to biological neuroendocrine differentiation in large cell carcinoma of the lung.     

Neuroendocrine carcinoma of the skin (Merkel cell carcinoma) in a black.

Neuroendocrine carcinoma of the skin is an uncommon, small-cell neoplasm most commonly found on white, sun-exposed skin. Diagnosis by clinical and histologic means may be difficult. Immunohistochemical and ultrastructural analysis are often required. Because of the aggressive nature of neuroendocrine carcinoma of the skin, prompt diagnosis and treatment are essential. We present the rare occurrence of a neuroendocrine carcinoma of the skin on sun protected skin in a black. Clinical, histologic, immunohistochemical, and ultrastructural features are reviewed, and therapeutic options are discussed.     

Primary neuroendocrine tumor of the breast

Adult neuroendocrine tumors may present with a wide range of clinical symptoms that share specific ultrastructural and biochemical features. A 63-year-old post-menopausal female patient was admitted to the hospital with a mass in her right breast and the diagnosis was primary neuroendocrine tumor of the breast. Although neuroendocrine tumors can originate in various parts of the body and breast carcinoma with neuroendocrine differentiation has been described, primary neuroendocrine tumor of the breast is very unusual. This case is now presented and the current literature is reviewed.     

Molecular and immune targets for Merkel cell carcinoma therapy and prevention

Merkel cell carcinoma (MCC) is a rare neuroendocrine carcinoma of the skin, for which the exact mechanisms of carcinogenesis remain unknown. Therapeutic options for this highly aggressive malignancy have historically been limited in both their initial response and response durability. Recent improvements in our understanding of MCC tumor biology have expanded therapeutic options for these patients, namely through the use of immunotherapies such as immune checkpoint inhibitors. Further elucidation of the tumor mutational landscape has identified molecular targets for therapies, which have demonstrated success in other cancer types. In this review, we discuss both current and investigational immune and molecular targets of therapy for MCC.     

Askin瘤1例报告并文献复习

 通过一例手术切除，光镜、电镜证实的Askin瘤，结合文献复习，就其诊断标准，临床特征、鉴别诊断要点，治疗原则进行讨论。     

皮肤麦克细胞癌四例临床病理分析

作者通过对４例罕见的皮肤麦克细胞癌进行临床病理观察研究，结合文献复习，认为此癌多见于中老年妇女，全身各部位均可发生，以头颈部多见，区域淋巴细胞转移率高，免疫组化染色显示，肿瘤细胞角蛋白，上皮膜抗原Ｓ１００阳性，电镜观察发现肿瘤细胞胞浆基质中有多少不等的神经内分泌颗粒，分布弥散无规律，观察结果表明此癌来源于上皮组织，并且具有向神经内分泌方向分化的特点。     

肝脏转移性神经内分泌癌的CT表现

目的 总结肝脏转移性神经内分泌癌的CT表现,探讨肝脏转移性神经内分泌癌的影像学特征,提高肝脏转移瘤的诊断能力.方法 回顾性分析肝脏转移性神经内分泌癌CT的影像学表现,归纳其影像学特征.结果 肝脏转移性神经内分泌癌CT表现为等密度或稍低密度占位,肿瘤坏死囊变区域较小.尤其是瘤灶直径＜2cm时,肿瘤多呈均质改变;瘤灶直径＞3 cm时,少部分瘤灶可出现坏死囊变.对比强化扫描,不含坏死成分的瘤灶动脉期呈均匀强化,门脉期密度呈等密度为主或呈相对低密度,延时期呈相对低密度.结论 肝脏转移性神经内分泌癌的多层螺旋CT影像学表现具有一定的特征性,可为临床的鉴别诊断提供帮助.     

The use of antikeratin antibodies in the immunohistochemical distinction between neuroendocrine (Merkel cell) carcinoma of the skin, lymphoma, and oat cell carcinoma

Paraffin sections of formalin-fixed tumor samples from 26 patients with neuroendocrine (Merkel cell) carcinoma of the skin (NECS) were studied immunohistochemically with three monoclonal antibodies to low molecular weight keratin (MAB-K) and with antibodies to leukocyte common antigen (LCA), neurofilament (NF), neuron-specific enolase (NSE), S100 protein (S100), and chromogranin (CGN), to investigate the relative diagnostic value of these antibodies. Samples from 20 lymphomas, 10 non-oat cell undifferentiated carcinomas, 10 oat cell carcinomas, and 10 melanomas served as controls. Keratin was found in 25 of the 26 NECS and in all undifferentiated and oat cell carcinomas. A ball-like immunostaining for keratins, resembling an inclusion body was seen only in cases of NECS and some carcinoids. Neurofilament, NSE, and CGN were expressed by fewer NECS than was keratin and all NECS were negative for LCA and S100. None of the lymphomas and melanomas contained detectable keratin, NF, NSE, or CGN. Only the lymphomas stained with LCA. Only the melanomas were S100-positive. It is concluded that keratin is the most useful single discriminating marker in the separation of neuroendocrine (Merkel cell) carcinoma of the skin from lymphoma, melanoma and, when the characteristic inclusion-like pattern is seen, from metastatic oat cell carcinoma.     

Pulmonary neuroendocrine tumors: incidence and prognosis of histological subtypes. A population-based study in Denmark

Pulmonary neuroendocrine tumors are currently considered to consist of three grades of malignancy, ranging from typical and atypical carcinoids to large-cell neuroendocrine carcinoma and small-cell carcinoma. The study reported here is the first population-based study of the demographics of patients with neuroendocrine tumors grouped by histological subtype. A cancer registry-based analysis of patients in Denmark in whom bronchial neuroendocrine tumor was diagnosed in 1978-97 was performed and the patients were followed up to 31 December 1999. Typical carcinoid was diagnosed in 105 patients, atypical carcinoid in 192, large-cell neuroendocrine carcinoma in 50 and small-cell carcinoma in 11,998. The recorded incidence of neuroendocrine tumors other than small-cell carcinoma increased by twofold among men (from 0.24 to 0.53 per 100,000 inhabitants per year) and by threefold in women (from 0.14 to 0.41 per 100,000 inhabitants per year) during the study period, while the incidence of small-cell carcinoma decreased among men and levelled off among women. The prognosis of patients with bronchial neuroendocrine tumors varied with the degree of malignancy; the 5-year survival rate ranged from 87% for patients with typical carcinoids, to 44, 15 and 2% for patients with atypical carcinoids, large-cell neuroendocrine carcinoma and small-cell carcinoma, respectively. In Denmark, the incidence of neuroendocrine tumours is increasing. Our findings support the pathological categorization of neuroendocrine tumors into three grades of malignancy. More research is needed to establish the etiological factors in the development of pulmonary neuroendocrine tumors.