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.     

Skull base surgery for the management of deeply invasive scalp cancer

Skin cancer involving the scalp is a common malignancy in the "sun belt areas of the United States." Most early lesions are well managed by primary care physicians and dermatologists. Occasionally we encounter basal cell, squamous cell, and rarely Merkel cell carcinomas that have failed local therapy and present with large tumors invading full thickness scalp, calvarium, and even underlying dura. We describe our experience with 52 such tumors and illustrate their resections and reconstruction. For full thickness lesions we generally do a wide field resection of skin and underlying calvarium followed by dural resection. Reconstruction is usually with dural replacement, calvarial reconstruction with titanium mesh, and cutaneous reconstruction with a musculocutaneous free flap or muscular free flap with an overlying skin graft. Complications, survival rates, and recurrence rates will be presented.     

Primary Merkel Cell Carcinoma of the Submandibular Gland: When CK20 Status Complicates the Diagnosis

Merkel cell carcinoma is a neuroendocrine tumor that occurs predominantly on the sun-exposed skin, with rare cases in the extracutaneous sites. It represents one of the extremely rare malignant neuroendocrine tumors of the salivary glands. We report a case of primary Merkel cell carcinoma of the right submandibular gland. The preoperative diagnosis was doubtful and the definitive histological diagnosis proved to be very difficult considering the extreme rarity of this tumor. The intraoperative evaluation of the macroscopic characteristics of the lesion led to an elective lymph node dissection. The extreme aggressiveness of the disease has resulted in the necessity of a new post-operative staging and in a multimodal treatment. This is the first primary submandibular gland Merkel cell carcinoma described in the literature. Differential diagnosis may be challenging and proper hematoxylin-eosin staining and immunohistochemical studies are mandatory.     

Immunological studies on the occurrence and properties of chromogranin A and B and secretogranin II in endocrine tumors

We investigated a variety of endocrine tumors for the presence of chromogranins A and B and secretogranin II. These antigens were identified by one- and two-dimensional immunoblotting and in some cases by immunohistochemistry. An antigen corresponding in electrophoretic behavior to adrenal chromogranin A was present in all types of tumors, including insulinomas, oat cell carcinomas, and Merkel cell tumors of the skin. Chromogranin B had a much more limited distribution. This antigen could not be detected in parathyroid adenomas, oat cell carcinomas, or Merkel cell tumors, either by immunoblotting and immunohistochemistry. The occurrence of secretogranin II was similar to that of chromogranin B, with the exception of a positive reaction in Merkel cell tumors. In benign pheochromocytomas, all three antigens were found consistently; whereas in two of three malignant pheochromocytomas, chromogranin B was absent. Our study establishes that in most cases chromogranins and secretogranin in tumors are identical to the adrenal antigens, but that these antigens are not always stored together. Chromogranin A is the most widely distributed marker for endocrine tumors.     

Absence of Merkel cell polyomavirus in primary parotid high-grade neuroendocrine carcinomas regardless of cytokeratin 20 immunophenotype

High-grade neuroendocrine carcinoma of the salivary glands is a rare malignancy that can be difficult to distinguish from metastatic neuroendocrine (Merkel cell) carcinoma of the skin, which often occurs on the head and neck and may metastasize to lymph nodes in or adjacent to salivary glands, particularly the parotid gland. As the 2 tumors have morphologic and immunophenotypic overlap, additional diagnostic tools may be clinically useful. Merkel cell carcinoma is known to harbor Merkel cell polyomavirus in up to 80% of cases. However, the presence or absence of this virus in salivary gland neuroendocrine carcinomas has not been investigated. We evaluated 7 primary salivary gland high-grade neuroendocrine carcinomas (all from the parotid) for the virus by both immunohistochemistry (CM2B4 clone) and real-time polymerase chain reaction directed against the conserved small T antigen. Five of the tumors had small cell morphology, and 2 had large cell morphology. All were either chromogranin and/or synaptophysin positive. Four of the 5 small cell (80%) and 1 of the 2 large cell (50%) carcinomas were cytokeratin 20 positive. All but 1 case had cervical lymph node metastases at presentation. Merkel cell polyomavirus T antigen was not detected in any of the 7 tumors, either by immunohistochemistry or by polymerase chain reaction with adequate controls. These observations suggest that primary parotid high-grade neuroendocrine carcinoma arises from a biological pathway that is different from that of cutaneous Merkel cell carcinomas. Furthermore, viral testing may aid in distinguishing the 2 tumor types, as a positive result would favor a metastasis.     

Merkel Cell Carcinoma of the Maxillary Sinus: An Unusual Presentation of a Common Tumor

Merkel cell carcinoma is most commonly seen in the skin of sun exposed areas, particularly the head and neck and is associated with Merkel cell polyomavirus. Merkel cell carcinoma at an extracutaneous mucosal site of the head and neck is rare. We report a case of a 74-year-old women who presented with an enlarging thyroid mass found to be neuroendocrine carcinoma consistent with Merkel cell carcinoma (positive for synaptophysin, chromogranin, CK20). Subsequent work up revealed a maxillary sinus mass with extension into the nasal cavity. Biopsy was diagnostic for Merkel cell carcinoma (positive for synaptophysin, chromogranin, CK20 and Merkel cell polyomavirus). There are only case reports and small case series of Merkel cell carcinoma arising in the mucosal sites of the head and neck most commonly in the oral cavity, rarely the sinonasal mucosa. Merkel cell carcinoma metastasizing to the thyroid has only been reported in three other case reports, all from skin primaries. In addition to our case, we review the literature of extracutaneous sinonasal Merkel cell carcinoma and metastases to the thyroid.     

Merkel cell carcinoma: improved outcome with adjuvant radiotherapy

BACKGROUND: Merkel cell carcinoma is an aggressive primary cutaneous neuroendocrine carcinoma. Patients remain at high risk of locoregional and distant relapse despite treatment. Most studies support the incorporation of locoregional adjuvant radiotherapy in reducing the risk of relapse. METHODS: Between 1980 and 2002, 86 patients diagnosed with Merkel cell carcinoma were treated with curative intent at Westmead Hospital, Sydney. Multivariate analysis was performed using Cox regression analysis. Disease-free survival and overall survival was calculated using Kaplan-Meier survival curves. RESULTS: Median age at diagnosis was 75 years (range 46-89 years) in 49 men and 37 women. Median duration of follow up was 31 months (range 6-153 months). Fifty-one (59%) patients presented with a primary lesion, 19 (22%) with a primary lesion and clinical nodal disease and 16 (19%) with lymph node metastases from an unknown primary. A total of 47 of 86 (55%) relapsed with regional nodal relapse, the commonest site of first relapse. Local relapse was similar for patients undergoing surgery (5/37; 14%) compared with surgery and adjuvant radiotherapy (3/25; 12%). Nodal relapse occurred in 14 of 36 (37%) treated with surgery compared with 7 of 38 (18%) patients treated with surgery and adjuvant radiotherapy. Patients treated with surgery and adjuvant radiotherapy experienced a better median disease free survival compared to those undergoing surgery alone (10.5 months vs 4 months; P < 0.01). The 5-year overall and disease-free survival rate for the entire study population was 47% and 25%, respectively. Twenty-six patients (30%) died as a result of Merkel cell carcinoma. CONCLUSION: Merkel cell carcinoma is an aggressive skin cancer. The addition of adjuvant radiotherapy markedly improves regional control rates and should be considered best practice.     

上尿路罕见肿瘤2例报告及文献复习

目的：探讨上尿路罕见肿瘤的诊治和预后。方法：回顾性分析2007年2月和12月收治的同时同侧肾及肾盂透明细胞癌和原发输尿管鳞状细胞癌患者各1例的临床资料,并结合文献进行总结。结果：2例患者术前未能明确诊断,实施了探查性手术,成功切除肿瘤,术后至今无复发或转移。结论：同时同侧‘肾及肾盂透明细胞癌和原发输尿管鳞状细胞癌均属罕见病例,但有其特点,可通过病史、辅助检查等初步与移行细胞癌等常见肿瘤相鉴别,从而选择恰当的治疗方式。预后有待进一步随访。     

Eccrine and squamous differentiation in Merkel cell carcinoma. An immunohistochemical study

Of the 42 Merkel cell carcinomas that we studied, two showed numerous tubular structures within sheets and nests of small cells. The small cells stained for both neuron-specific enolase and keratin. The keratin decorated a dot-like paranuclear structure. The ducts stained positively for carcinoembryonic antigen (CEA) and CF-1 (cystic fibrosis-1, a monoclonal antibody that only stains eccrine duct and acrosyringium). Electron microscopy performed on one case showed cytoplasmic dense-core neurosecretory granules and intercellular lumina lined by cells containing microvilli. These ultrastructural and immunohistochemical features support the concept of eccrine differentiation in these tumors. A third case contained foci of typical keratinizing squamous cell carcinoma admixed with sheets of small cells. The immunohistochemical and ultrastructural characteristics of this tumor were essentially similar to those of a conventional Merkel cell carcinoma. Our findings suggest that Merkel cell carcinomas, similar to neuroendocrine tumors from other anatomic sites arise from a primitive totipotential stem cell that has the capacity to differentiate along different cell lines.     

Basal Cell Carcinoma of the Dorsum of the Hand

Although extremely frequent elsewhere on the body, basal cell carcinomas are infrequent on the hands (< 1% of all basal cell carcinomas). Chronic sun exposure is considered as the main etiologic factor for its development but it does not explain low frequency of hand involvement. Presented here is a series of seven patients with basal cell carcinoma of the hand. All were treated by surgery alone. Clinical presentation was classical: a slowly growing chronic ulceration. None of the patients was chronically exposed to chemical agents but two of them developed their tumour in previously irradiated areas, focusing on this specific etiologic factor for basal cell carcinomas of the hands.     

Pathology of malignant skin tumours

The skin gives rise to a diverse spectrum of malignant tumours derived from the varied constituents of the epidermis and dermis. It is possible to discuss only a few of these in this article; the more common lesions derived from the epidermal keratinoctyes (basal and squamous cell carcinomas) together with melanomas (derived mainly from epidermal melanocytes) are presented. Some rarer but biologically aggressive tumours such as Merkel cell carcinoma and angiosarcoma are also discussed. Our understanding of the molecular biology of cutaneous tumours continues to evolve rapidly particularly for melanomas and in the coming years genetic profiling of individual tumours with targeted therapy is likely to play an important role in management.     

Small cell carcinoma of the major salivary glands: clinicopathologic study with emphasis on cytokeratin 20 immunoreactivity and clinical outcome

Small cell carcinomas arising in salivary glands, extremely rare high-grade malignant tumors, are subclassified into neuroendocrine and ductal types. The neuroendocrine type may be segregated further into Merkel cell and pulmonary varieties according to cytokeratin 20 immunoreactivity. Whether subclassification of this tumor group has any biologic or clinical significance is not known. We examined 15 cases (11 men, 4 women; mean age, 66.5 years) of small cell carcinoma of major salivary glands from a single institution and analyzed their clinicopathologic profiles, including immunohistochemical features and prognostic factors. Three fourths of small cell carcinomas showed cytokeratin 20-positive immunostaining, often with a paranuclear dotlike pattern of reactivity. All tumors were immunoreactive for at least 2 of 6 neuroendocrine markers examined, and 6 tumors were also positive for neurofilament, with a paranuclear dotlike pattern. Postoperatively, 9 patients developed metastatic disease, and 10 patients died of disease 2 to 45 months (mean, 15.9 months) after diagnosis. By log-rank analysis, overall survival was reduced significantly for patients with a primary tumor larger than 3 cm in diameter (P = 0.032), negative immunostain reaction for cytokeratin 20 (P = 0.012), and decreased immunoreactivity for neuroendocrine markers (P = 0.034). These results indicate that small cell carcinoma of major salivary glands is a highly aggressive tumor, although the prognosis may be better than for extrasalivary neoplasms. Our data also suggest that most salivary gland small cell carcinomas exhibit neuroendocrine differentiation. Immunohistochemical expression of cytokeratin 20 can be used to classify salivary small cell carcinomas into Merkel cell and pulmonary types and may have prognostic significance.     

Racial and Ethnic Healthcare Disparities in Skin Cancer in the United States: A Review of Existing Inequities,Contributing Factors,and Potential Solutions

Objective Racial and ethnic health disparities affect the diagnosis and management of melanoma and nonmelanoma skin cancers, leading to deleterious outcomes. Non-Hispanic White patients make up the majority of skin cancers cases, yet racial and ethnic minorities have poorer prognoses and outcomes. The skin cancer literature is fragmented with regards to potential contributors to these healthcare disparities. In this article, we provide a comprehensive review of the skin cancer literature to briefly quantify racial and ethnic inequities, highlight contributing factors, and propose practical changes that can be made.MethodsA PubMed search was completed to identify articles related to racial and ethnic health care disparities in the context of melanoma, basal cell carcinoma, squamous cell carcinoma, Merkel cell carcinoma, and dermatofibrosarcoma protuberans.ResultsRelative to non-Hispanic White patients, patients of racial and ethnic minorities have differing clinical presentations of skin cancers and genetic risk factors. Insurance, access to specialty care, cultural beliefs, and available educational resources further contribute to racial and ethnic disparities.LimitationsWe are limited to the level of detail provided in the existing literature, and at some times are unable to distinguish race of Hispanic populations. We also acknowledge that there are different nationalities grouped under these broad labels as well as multi-racial populations that may not be accounted for.ConclusionAwareness of and familiarization with innate factors and potentially more modifiable contributors can help inform efforts to close the observed gap in racial and ethnic inequities.     

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.     

Skin Cancer in Transplant Recipients,Out of the Woods. Scientific Retreat of the ITSCC and SCOPE

The International Transplant Skin Cancer Collaborative (ITSCC) is an organization of more than 300 members dedicated to the study and care of skin changes that develop in solid‐organ transplant recipients. This group of medical and surgical dermatologists, transplant surgeons and basic science researchers was formed to better understand the basic science of transplant dermatology, and to work collaboratively to address the clinical challenges in this patient population. Transplant patients have an ～100‐fold increased risk of developing cutaneous squamous cell carcinoma than the general population and are also at an increased risk of developing basal cell carcinoma, melanoma, Merkel cell carcinoma and Kaposi's sarcoma. In October 2010, ITSCC and its European counterpart Skin Care in Organ Transplant Patients Europe (SCOPE) held a joint biennial 4‐day scientific retreat in the woods near Essex, Massachusetts. In this meeting report we provide an up‐to‐date distillation of the novel findings presented in the 21 oral abstracts, at the tumor board and within the working groups.     

Imaging characteristics of papillary renal cell carcinoma by computed tomography scan and magnetic resonance imaging

AIM: To analyse the differences in the patterns between clear and papillary renal cell carcinomas using magnetic resonance imaging (MRI) and dual-phase helical computed tomography (CT). METHODS: We examined seven patients with papillary renal cell carcinoma, and six with clear cell carcinoma. The highest attenuation value of tumors in the corticomedullary phase (CMP) and the excretory phase (EP) was measured using the observer-defined region of interest (ROI). MRI consisted of T1-weighted and T2-weighted spin-echo imaging. RESULTS: All five tumors except for one with papillary renal cell carcinoma showed homogenous hypointensity, but all six tumors with clear cell carcinoma showed heterogeneous hyperintensity on their T2-weighted images. In the CMP, the mean CT numbers of the papillary renal cell carcinomas were significantly lower than those of the clear cell carcinomas. The mean enhancement of the papillary renal cell carcinomas in the CMP and the EP was significantly lower than that of the clear renal cell carcinomas. The mean CT numbers of the clear cell carcinomas in the CMP were markedly increased from those on the unenhanced CT; those in the EP were decreased gradually. But the mean CT numbers of the papillary renal cell carcinomas in the EP were still slightly more increased than those in the CMP. The enhancement patterns of the papillary renal cell carcinomas in the CMP and the EP were homogenous, but those of the clear cell carcinomas were heterogeneous. CONCLUSIONS: We can speculate the differential diagnosis from clear to papillary renal cell carcinoma using MRI and dual-phase helical CT.     

Angiogenesis and skin carcinomas with skull base invasion: a case-control study

BACKGROUND: Some skin carcinomas may be very aggressive. Intensity of angiogenesis, measured by intratumoral vessel density using expression of CD34, has been associated with tumor aggressiveness. In this study, the expression of CD34 in basal cell carcinomas ( BCCs) and squamous cell carcinomas (SCCs) with skull base invasion was compared with that in tumors with good outcome. METHODS: Expression of CD34 was graded as mild, moderate, and intense, in 24 BCCs and 11 SCCs with skull base invasion. The control group included 23 BCCs and 10 SCCs. RESULTS: Intense expression of CD34 was noted in 25.00% of BCCs with skull base invasion, compared with 4.35% in the control group (p =.058). Regarding SCCs, intense expression of CD34 was found in 54.55% of aggressive tumors, compared with 10.00% in the control group (p =.133). CONCLUSIONS: A trend toward denser microvascular angiogenesis was observed in both BCCs and SCCs with skull base invasion compared with less aggressive controls.     

Rising incidence of Merkel cell carcinoma

Abstract

Merkel cell carcinoma (MCC) is a rare, aggressive, skin cancer of obscure histogenesis, the incidence of which is rising. There is no consensus on the optimal treatment. Our aim was to evaluate the staging, investigation, treatment, and follow-up of MCC in eastern Denmark, and to investigate the incidence. We suggest guidelines for treatment. First we reviewed the medical records of 51 patients diagnosed with MCC from 1995 until 2006 in eastern Denmark. The nation-wide incidence of MCC was extracted from the Danish Cancer Registry for the calculations for the period 1986-2003. We reviwed published papers about MCC based on a MEDLINE search. Fourteen of the 51 patients developed recurrence, and 37 (73%) died during the study period. Mean follow-up was 13 months (range 1–122). A total of 153 patients were identified in the Danish Cancer Registry, and showed that incidence rates had increased 5.4 fold over the 18 year period from 1986 until 2003. Rates were highest in people over the age of 65. Recommended treatment with curative intent includes excision of the primary tumour with wide margins, excision of the sentinel node, computed tomogram (CT) or positron emission tomography (PET) of the thorax and abdomen, and adjuvant radiotherapy to the surgical bed. In the case of advanced disease, systemic palliative chemotherapy remains a possibility. There is a need for prospective multicentre evaluation of staging investigations and treatment of MCC.     

Poorly differentiated neuroendocrine carcinoma of the breast with Merkel cell features

Neuroendocrine carcinoma of the breast is a rare tumor subtype comprising less than 1% of breast cancers in the United States. Merkel cell features within this rare subtype are even rarer. We report a neuroendocrine breast carcinoma with Merkel cell features. The patient underwent breast conservation therapy and a sentinel lymph node biopsy. Unfortunately, the tumor was extremely aggressive and at 5 weeks postoperatively she presented with widely metastatic disease. Due to the aggressive nature of this tumor, we reviewed the literature and treatment options for this rare variant of a rare subtype.