Lymph node Merkel cell carcinoma with no evidence of cutaneous tumor--report of two cases

We report two cases of Merkel cell carcinoma within inguinal and axillary lymph nodes, respectively, showing no clinico-pathologic evidence of a primary (extranodal) tumor; one of our patients was alive with no evidence of disease five years and ten months after the surgical excision of the neoplasm with no postoperative chemotherapy. The diagnosis of nodal Merkel cell carcinoma needs to be supported by a careful immunohistochemical study: in fact, cytokeratin- and neurofilament-positive paranuclear "dots", as well as epithelial antigens and neuroendocrine markers may be variably expressed in tumor cells, thus requiring the application of a complete antibody panel. In the presence of a nodal Merkel cell tumor, an exhaustive clinico-radiologic search for a primary tumor must be carried out. After the exclusion of any reasonable starting point of the neoplasm, a provisional diagnosis of "primary" nodal Merkel cell carcinoma may be acceptable; since a primary extracutaneous tumor is expected to follow a less aggressive course than a metastatic one, follow-up data may provide indications as to the truly extracutaneous origin of Merkel cell carcinoma.     

Pagetoid Merkel cell carcinoma: epidermal origin of the tumor

We report a case of intraepidermal Merkel cell carcinoma which occurred on the face of a 76-year-old white male. This slow-growing tumor was mostly confined in the epidermis and pilosebaceous apparatus where tumor cells spread in a pagetoid fashion forming tumor cell nests. Histologically it resembled a superficial spreading melanoma. A heavy lymphocytic infiltration was seen beneath the epidermal lesion as is often seen in pagetoid melanomas. Histochemical and ultrastructural features such as the presence of cytokeratin 20, synaptophysin, neuron specific enolase, desmosomes, and dense cored granules confirmed the diagnosis of Merkel cell carcinoma. Occasional mitotic cells and many apoptotic cells were found in the tumor. Dylon positive, amyloid depositions were seen in the lower epidermis and papillary dermis; they were probably derived from apoptotic tumor cells. It was thought that apoptosis limited the speed of growth of this tumor. We believe that this is probably the most convincing case of intraepidermal Merkel cell carcinoma originating from epidermal Merkel cells or its precursors (stem cells).     

Merkel cell carcinoma of the skin

Primary neuroendocrine carcinoma of the skin or Merkel cell carcinoma is an aggressive primary neoplasm. It is commonly seen in the elderly, on the head, neck and extremities, where it can mimic a benign or less malignant skin tumour. Pathological examination shows a generally dense growth of small dark cells, with immunohistochemical evidence of neuroendocrine differentiation. The microscopic appearance is very similar to metastatic oat cell carcinoma from the lung and this must be excluded by clinical means and appropriate imaging studies. In this study we present 13 new cases of Merkel cell carcinoma (the largest published series in the UK) and summarize 214 cases from the literature in which the survival data are given. In our series, 5 of 13 patients died from spread of the Merkel cell carcinoma. From this and other studies, it appears that early diagnosis and wide local excision may be the only way to prolong survival. No other adjuvant therapy has proved effective.     

Solitary choroidal metastasis as the first sign of metastatic lung carcinoid

The identification of malignancies associated with transplantation has led to enhanced vigilance and care in these patients, as well as insight into the pathogenesis of select malignancies. We report a case of Merkel cell carcinoma, an uncommon cutaneous malignancy of neuroendocrine origin, diagnosed in a 65-year-old Caucasian man 6 years after renal transplantation. While it is well known that transplant patients are at increased risk for squamous cell carcinomas of the skin, other types may also have an increased frequency. We suggest that Merkel cell carcinoma could have an increased incidence in the transplant population.     

Peritonitis due to CDC coryneform group A-4 in a patient undergoing continuous cycling peritoneal dialysis

A rare case is described of Merkel cell carcinoma of the cheek arising in a cutaneous neurofibroma in a patient with Recklinghausen neurofibromatosis. The relevant literature is reviewed.     

Percutaneous biopsy of the thoracic and lumbar spine: transpedicular approach under fluoroscopic guidance

BACKGROUND: Merkel cell carcinoma (MCC) is a rare, aggressive, cutaneous neoplasm. The primary form of initial treatment is wide surgical excision. The use of Mohs micrographic surgery as the primary form of treatment in MCC has been controversial. The course of MCC is often aggressive, with early metastasis, widespread disease, and death. Despite the poor prognosis, spontaneous regression has occasionally been reported. OBJECTIVE: We describe the clinical course of two patients with Merkel cell carcinoma who underwent treatment with Mohs micrographic surgery for the primary MCC. Metastases were excised in the first case and spontaneously regressed in the second. Both patients are without clinical disease at the time of this report. METHODS: Histopathology, clinical records, and the current literature are reviewed. RESULTS: One patients was without recurrence of MCC for 13 years of follow-up. The other patient experienced clinical spontaneous remission after nodal spread of the disease, with no recurrence for 18 months after clinical remission and 24 months after surgery. CONCLUSION: The treatment of Merkel cell carcinoma with Mohs micrographic surgery (MMS) has been successful for the control of primary skin disease, and is at least comparable to wide excision. Spontaneous regression may occur in the course of this usually relentless and aggressive disease. The explanation for spontaneous regression of MCC is unknown.     

Merkel cell tumor

Merkel cell cancer is a rare carcinoma arising from the neuroendocrin cells of the skin. The diagnosis is based on the clinical behaviour, histopathologic and ultrastructural findings and immunohistochemical results. An unusual case of Merkel cell carcinoma is presented. Mass from the umbiculus and a right inguinal lymph node was excised in a 63-year-old female. The histologic features of a typical, primitive small cell tumor combined with the immunohistochemical evaluations established the diagnosis. Rare polynuclear giant cells were focally present in our case. Patient was treated with combination of chemotherapy (Cisplatin, Etoposid) and radiotherapy. Control examinations showed complete respond. One year later metastasis developed. Resection of all known metastasis were performed. Two months after the laparotomy she died of metastatic disease. The autopsy did not reveal any other primary tumor. The capricious nature of the clinical course and the differences between this tumor and other carcinomas is emphasized.     

The role of radiation therapy and chemotherapy in the treatment of Merkel cell carcinoma

BACKGROUND: Merkel cell carcinoma is a rare and highly aggressive skin tumor. The purpose of this study was to determine the role of radiation therapy and chemotherapy in the treatment of patients with Merkel cell carcinoma. METHODS: A retrospective analysis of 27 patients treated at Rabin Medical Center in Israel is presented, focusing on the treatment details. Data for 40 patients (the authors' 27 patients and an additional 13 patients from the Israeli Cancer Registry), were analyzed for prognostic factors using univariate and multivariate analyses. RESULTS: Univariate analyses revealed regional lymph node involvement and the coexistence of a second primary tumor as unfavorable prognostic factors. On multivariate analysis, only lymph node involvement showed borderline statistical significance. Radiation therapy was highly effective when given as consolidation after surgery or chemotherapy. In 11 patients irradiated effectively, only 1 (9%) in-field recurrence occurred. Radiation therapy yielded responses in 15 of 15 measurable sites (5 complete responses and 10 partial responses). Chemotherapy produced responses in 18 of 26 patients (69%), mostly complete (41%). However, in the absence of radiation therapy, the responses were short lived. CONCLUSIONS: These data support the use of combined treatment with chemotherapy followed by radiation therapy for patients with advanced locoregional Merkel cell carcinoma. In patients with metastatic disease, chemotherapy as well as radiotherapy can provide effective palliation. Further large scale investigations are warranted to confirm this approach.     

Merkel cell carcinoma: primary cutaneous neuroendocrine tumor

Merkel cell carcinoma is a neuroendocrine primitive tumor of the skin. We report a case who develops node and visceral metastasis, and dead. The clinical presentation, diagnosis, histology, immunocytochemistry, treatment and prognosis of this tumor will be discussed.     

Merkel cell tumor. Report of case and treatment with octreotide

Merkel cell carcinoma is a rare neuroendocrine tumor of the skin. Prognosis is very poor particularly when systemic disease is present. Surgery, chemo and/or radiotherapy treatment are not able to guarantee long survival and quality of life is also very poor. We know that neuroendocrine tumor can be in possession of receptors for somatostatin; during the past years, these receptors have been demonstrated in vivo by octreoscan. We report a case of a patient suffering from metastatic Merkel cell carcinoma; because he was elderly, neither chemotherapy nor radiotherapy were possible as a consequence of the explosion of the disease after surgery. The presence of receptors for somatostatin analogues (octreoscan) allowed treatment with octreotide causing the immediate disappearance of metastasis. After ten months of treatment the patient presents a complete remission of disease. Octreotide, the most important somatostatin analogue, represents a primary role in the neuroendocrine tumor management; the drug also lacks of toxicity.     

Speedy backcrossing through in vitro fertilization, using pre-pubertal superovulation and neonatal death dependent on genetic background in angiotensinogen-deficient mice

We report a case of neuroendocrine (Merkel cell) carcinoma (NC) of the skin, associated with a trichilemmal cyst, showing pagetoid spread into the trichilemmal epithelium. The association of the two lesions may strengthen the hypothesis that NC originates from pluripotent stem cells of adnexal epithelium.     

Neuroendocrine (Merkel cell) carcinoma of the oral mucosa: report of a case with immunohistochemical study and review of the literature

Merkel cell carcinoma (Mcc) is an uncommon and aggressive tumour with neuroendocrine features that occur predominantly in the head and neck region. The rarity of this tumour, especially when it arises in the oral mucosa, makes both early identification and standardisation of treatment difficult, particularly as regards complementary treatment. The availability of monoclonal antibodies with restricted specificity for some antigens thought to be related to neuroendocrine carcinomas, such as Merkel cell carcinoma, and ultrastructural studies offer some new leads to investigation. This has allowed, a greater number of these tumours to be discovered, thereby increasing the chances of effective management. A case of Mcc of the floor of the mouth is reported, together with the results of cytokeratin, neuron specific enolase and chromogranin immunohistochemistry.     

Cytokeratin 20 is a general marker of cutaneous Merkel cells while certain neuronal proteins are absent

Merkel cells are difficult to identify in tissue sections. Previous studies have used cytokeratins (CK) 8, 18, and 19 as histologic markers of Merkel cells. However, these CKs are also expressed in some outer root sheath keratinocytes and some early fetal epidermal cells and thus are not truly specific of Merkel cells in general. Using selective antibodies against a newly described CK, number 20--originally found in intestinal epithelium and Merkel cell carcinomas--in comparison to a key protein of neuroendocrine cells, chromogranin A, we established CK 20 as a specific Merkel cell marker in skin of humans, pigs, and mice. CK 20 seems to be an even more general and sensitive Merkel cell marker as compared to CgA. In double-labeling experiments with stratified-squamous epithelial CK (numbers 5 and 13-17) and simple epithelial CK (numbers 8, 18, and 20) antibodies evaluated by confocal laser scanning microscopy, no cell expressing CKs of both types (i.e., no cell of so-called "transitional" character between Merkel cells and keratinocytes) was identified in human skin. In addition, various neuronal markers present in Merkel cell carcinomas including neurofilaments, peripherin, nerve growth factor receptor, and neuronal cell adhesion molecule appear to be absent in normal Merkel cells. Thus, Merkel cells exhibit a distinct and unique marker profile, with CK 20 being of particularly high value in various species.     

Prognostic evaluation of lymph node metastasis in thoracic esophageal cancer--an analysis of 212 cases

The presence of immunoreactive neurofilament proteins has previously been reported in Merkel cell carcinomas but not in normal human epidermal and dermal Merkel cells. We have studied the immunoreactivity of epidermal Merkel cells for neurofilament triplet proteins (68 KD, 70 KD, 160 KD, 200 KD), using epidermal sheets prepared from the plantar skin of human adults, which enabled us to survey large numbers of Merkel cells. Neurofilament protein 200 KD-positive cells were readily identified, while neurofilament protein 68 KD-, 70 KD- and 160 KD-positive cells were largely absent. 200 KD-positive cells in the epidermis were confirmed to represent Merkel cells by a sequential immunoenzyme labeling for the simple epithelial type cytokeratin (No. 8). 200 KD-positive cells were 5.9% of the total number of epidermal Merkel cells. Despite a heterogeneous expression of neurofilament protein subspecies between the normal and transformed Merkel cells, the presence of neurofilament proteins in epidermal Merkel cells may link them to Merkel cell carcinomas.     

A preventive oncologic program for detection of early stages of endometrial carcinoma and its precursors

Merkel cell carcinoma of the skin is a rare malignant tumour first described in 1972 by Toker. The optimal management of this disease has not been clearly defined, especially that of advanced locoregional disease. Surgery, radiotherapy and chemotherapy have been advocated separately or in combination, with less-than-optimal results. Localized high-dose chemotherapy has never been tried, although it would seem to be the logical step forward.     

Calcium inflow of hamster Merkel cells in response to hyposmotic stimulation indicate a stretch activated ion channel

The aim of this study was to investigate the existence of the stretch activated ion channels in single Merkel cell using microfluorimetric techniques. Single Merkel cells were dissociated enzymatically from the touch domes in the cheek pouch mucosa of 4-8 week old golden hamsters. They were loaded with calcium (Ca2+) fluorescent indicator fura-2/AM. The increase in intracellular Ca2+ concentration ([Ca2+]i) of a single Merkel cell (quinacrine fluorescent cell) was induced by hyposmotic solution in normal Krebs solution, while it was not induced by Ca2+-free hyposmotic solution in Ca2+-free physiological solution. Gadolinium ion (10 microM) in normal Krebs solution partially blocked the increase in [Ca2+]i of Merkel cells induced by hyposmotic solution. Hence, this study revealed that stretch activated ion channels existed on the Merkel cell membrane.     

Correction of hypospadias

A case of Merkel cell carcinoma of the skin is described. It is a rare primary skin tumor originating within the dermis with an aggressive biologic behavior. Clinical presentation of these tumors are not sufficiently distinctive to allow the preoperative diagnosis. Wide surgical excision with postoperative irradiation to the local site and regional lymphatics is recommended as the therapy of choice. Indications for chemotherapy are discussed and the guidelines for an appropriated follow-up are reported.     

PET evaluation of therapeutic limb perfusion in Merkel's cell carcinoma

An 87-yr-old woman diagnosed with recurrent Merkel's cell carcinoma was treated with therapeutic limb perfusion and underwent PET scanning with 18F-fluorodeoxyglucose (FDG). PET studies were obtained before and after treatment to determine the response to the intervention. A baseline whole-body study was obtained to assess the extent and degree of disease activity. This was followed by a repeat PET scan 2 mo. later after treatment with isolated limb chemotherapy with high-dose melphalan and tumor necrosis factor-alpha. The initial scan demonstrated multiple foci of high FDG uptake in the left calf, a left supraclavicular lesion and also detected concurrent keratinizing squamous cell metastasis in the right axilla. A repeat PET study showed complete metabolic resolution of the lesions in the left calf after treatment. FDG PET may be a useful technique for staging Merkel cell carcinoma and for assessing the tumor response after therapy of this rare tumor.     

Excision of selected skin tumours using Mohs' micrographic surgery with horizontal paraffin-embedded sections

Histological interpretation of frozen sections made during Mohs' micrographic surgery may be difficult, depending on the morphological and staining characteristics of the tumour and on the nature of the associated inflammatory infiltrate. We have employed an adaptation of micrographic surgery in which horizontal, formalin-fixed, paraffin-embedded sections were used to improve histological assessment in the excision of 18 non-melanoma skin tumours in which frozen sections had been or were likely to be unsatisfactory. We describe our experience of this method in the management of squamous cell carcinomas (11), extramammary Paget's disease (two), microcystic adnexal cell carcinomas (two), dermatofibrosarcoma protuberans (two), and primary cutaneous neuroendocrine carcinoma (Merkel cell carcinoma) (one). The use of horizontal paraffin-embedded sections lengthens the duration of the procedure but facilitates accurate assessment of histological sections in selected tumours.