Synchronous onset of multiple cutaneous neuroendocrine (Merkel cell) carcinomas localized to the scalp

Merkel cell carcinoma (MCC) is a rare aggressive neoplasm that typically presents as a solitary nodule or plaque on sun-exposed skin of the elderly. Although multiple MCC have been described, they are rare, and metastases must be excluded. We report a case of a 59-year-old white male who presented with abrupt onset of multiple small bluish papules on his frontal scalp. On low power, the tumor had the overall histological silhouette of a nodular basal cell carcinoma. However, because of the lack of an epithelial connection and the cell's cytomorphological features, a MCC was considered and was subsequently confirmed using immunohistochemical stains. The MCC described in this report is unusual in that it presented as multiple cutaneous lesions that arose synchronously, along with micrometastases to sentinel lymph nodes.     

Triphasic differentiations of Merkel cell carcinoma in primary and metastatic lesions

We present a rare case of Merkel cell carcinoma (MCC) with heterologous differentiation. The patient was an 86‐year‐old female patient with MCC who presented with a forearm skin tumor and left axillary lymph node swelling. Histopathologically, the malignant components of the primary and metastatic lesions showed the intermingled features of triphasic phenotype differentiation, which had distinct cell populations; MCC, sweat gland carcinoma (SGC) and malignant poorly differentiated spindle cells with myogenic differentiation were immunohistochemically showed. Moreover, an electron microscopic observation of the tumor cells revealed intracytoplasmic canaliculi and junctional structures that indicated ductal differentiation. To our knowledge, this is the first case of MCC admixed with SGC and sarcomatous components in both the primary and metastatic lesions. An immunohistochemical study, using several stem cell markers, indicated that the MCC arose from pluripotent epidermal stem cells.     

Cutaneous undifferentiated small (Merkel) cell carcinoma,that developed synchronously with multiple actinic keratoses,squamous cell carcinomas and basal cell carcinoma

Merkel Cell Carcinoma (MCC) is an uncommon undifferentiated neuroendocrine tumor, arising in skin mainly on sun-exposed areas. We present an unusual case of primary cutaneous undifferentiated small cell carcinoma that co-existed with six other lesions; 2 actinic keratoses, 3 squamous-cell carcinomas and a basal-cell carcinoma. HE stained sections revealed MCC located in the mid-dermis, co-existing with severe actinic keratosis. Immunohistochemically, the tumor cells reacted to cytokeratin 20, epithelial membrane antigen, chromogranin and neuron specific enolase. This is an unusual case of cutaneous MCC co-existing with six other different lesions. The concurrent development of MCC, squamous-cell and basal-cell carcinoma in the same patient indicates the pluripotent epidermal stem cell origin of these tumors. Further research is needed to enlighten the factors inducing this divergent differentiation.     

Merkel cell carcinoma: a clinicopathologic study with prognostic implications

BACKGROUND: Merkel cell carcinoma (MCC) is a frequently aggressive neuroendocrine malignancy of the skin that presents in sun-exposed areas on elderly patients. Although originally described over 30 years ago, many aspects of MCC remain to be defined. Of particular importance is the need to identify prognostic factors capable of predicting the biological behavior of these tumors. Knowledge of these factors may help in determining which patients require more aggressive treatment regimens. In this study, we examined 25 cases of MCC with an attempt to identify clinical, histopathological, or immunohistochemical features capable of predicting disease outcome. METHODS: Features that we evaluated in each case included age, gender, race, tumor location, tumor size, depth of invasion, growth pattern, lymphocytic infiltration, mitotic activity, ulceration, necrosis, vascular invasion, and perineural invasion. In addition, we examined neural cell adhesion molecule and cytokeratin-20 expression using immunohistochemical methods. RESULTS: We found that most patients were males (84%) with an average age of 74 years. The tumors were located on the head and neck (68%) and upper extremities (32%). Overall, 64% of the patients developed metastatic disease to regional lymph nodes or distant sites (average follow-up time of 21 months). Local recurrence was also common, occurring in 29% of the patients. The overall 1- and 2-year survival rates were 80 and 53%, respectively. Histopathological examination revealed tumors with an average size of 7.2 mm. Common features included invasion into the subcutaneous adipose tissue, solid growth pattern, tumor necrosis, and vascular and perineural invasion. Findings that had a statistically significant correlation with poor outcome included tumor size > or =5 mm (p = 0.047), invasion into the subcutaneous adipose tissue (p = 0.005), diffuse growth pattern (p = 0.040), and heavy lymphocytic infiltration (p = 0.017). The remaining findings, including the immunohistochemical results, did not correlate with disease outcome. Using logistic regression models, we show that depth of invasion and degree of lymphocytic infiltration are strong predictors of disease outcome. CONCLUSIONS: The current controversies regarding the treatment of early-stage MCC (i.e., localized disease) underscore the importance of identifying clinicopathological features capable of predicting tumor behavior. In this study, we have identified several prognostic features in MCC. Perhaps, these features may prove useful in identifying patients who require more aggressive treatment regimens.     

Merkel cell carcinoma: squamous and atypical fibroxanthoma-like differentiation in successive local tumor recurrences

Merkel cell carcinoma (MCC) is a rare, frequently lethal, primary neuroendocrine carcinoma of the skin. Histopathologically, it appears as a dermal nodule of small, undifferentiated malignant cells. Historically, MCC was considered to be an eccrine carcinoma. Recognition of its neuroendocrine features later led to the hypothesis that it arose from Merkel cells in the skin, although recent evidence revisits the question of an epithelial origin. We present a case of MCC arising on the temple of a 78-year-old male, in association with an actinic keratosis. Three years later, a local tumor recurrence showed a mixed malignancy comprising small cell neuroendocrine and large cell squamoid components. A further recurrence at the site two years later, after local radiotherapy, revealed a bizarre pleomorphic large cell morphology with retention of immunohistochemical features of a neuroendocrine carcinoma. Evolution to a bizarre pleomorphic large cell neoplasm has been recorded in malignant tumors treated by radiotherapy, but is unique for MCC. The association of this MCC with an actinic keratosis and the development of squamoid differentiation in a local recurrence support the link between MCC and epithelial neoplasia. In addition, its evolution to an atypical fibroxanthoma-like morphology is of interest, because some view atypical fibroxanthomas as bizarre variants of squamous cell carcinoma.     

CD56: a useful marker for diagnosing Merkel cell carcinoma

BACKGROUND: Merkel cell carcinoma (MCC) of the skin is an aggressive but rare malignant neuroendocrine tumor. For its pathological diagnosis, we use a panel of immunohistochemical markers, such as cytokeratin 20 (CK 20), epithelial membrane antigen (EMA), chromogranin A, neuron specific enolase (NSE), synaptophysin, and Leu7 (CD57) to demonstrate its epithelial and neuroendocrine features. CD56, or neural cell adhesion molecule (NCAM), has been demonstrated recently as the tumor marker of the pulmonary neuroendocrine cell system. Its expression in MCC, however, has still rarely been investigated. Furthermore, in such very few previous studies on NCAM expression in MCC, all the tumor cells were not necessarily demonstrated to express NCAM. OBJECTIVES: To study the immunoreactivity of CD56 in MCC, especially using a monoclonal antibody of a clone 1B6, different from those adopted in the previous reports. METHODS: We reexamined CD56 expression immunohistochemically in five MCC cases, along with the conventional panel of markers described above, using paraffin-embedded tissue sections. RESULTS: CD56 revealed the most diffuse and intense positive staining, which was noted along the cell borders, in all specimens compared with other neuroendocrine tumor markers. CONCLUSIONS: The results of our study indicate that CD56, especially a new monoclonal antibody (clone 1B6), is a useful immunohistochemical marker for MCC.     

Intraepidermal and dermal Merkel cell carcinoma with squamous cell carcinoma in situ: a case report with review of literature

Merkel cell carcinoma (MCC), a rare aggressive primary cutaneous neuroendocrine carcinoma, occurs on sun‐damaged skin, especially in the elderly. Its unique co‐expression of cytokeratin 20 (CK20) and neuroendocrine markers, including neuron‐specific enolase (NSE), is diagnostic. Most MCCs are located in the dermis, rarely has an intraepidermal component been reported. We report a case of MCC with an intraepidermal component admixed with squamous cell carcinoma in situ (SCCIS). We were able to identify the differences in the immunohistochemical expression pattern between that of the intraepidermal and the dermal components. Most intraepidermal neoplastic cells of MCC in this case showed a less intense immunoreactivity to CK20 and NSE compared to that of dermal neoplastic cells. This case reports an unusual occurrence of combined SCC and MCC that shows both intraepidermal and dermal components. Sirikanjanapong S, Melamed J, Patel R. Intraepidermal and dermal Merkel cell carcinoma with squamous cell carcinoma in situ: a case report and review of literature.     

S2k Guideline – Merkel cell carcinoma (MCC,neuroendocrine carcinoma of the skin) – Update 2022

Merkel cell carcinoma (MCC, ICD-O M8247/3) is a rare, malignant, primary skin tumor with epithelial and neuroendocrine differentiation. The tumor cells share many morphologic, immunohistochemical, and ultrastructural features with cutaneous Merkel cells. Nevertheless, the cell of origin of MCC is unclear. MCC appears clinically as a reddish to purple spherical tumor with a smooth, shiny surface and a soft to turgid, elastic consistency, usually showing rapid growth. Spontaneous and often complete regressions of the tumor are observed. These likely immunologically-mediated regressions explain the cases in which only lymph node or distant metastases are found at the time of initial diagnosis and why the tumor responds very well to immunomodulatory therapies even at advanced stages. Due to its aggressiveness, the usually given indication for sentinel lymph node biopsy, the indication of adjuvant therapies to be evaluated, as well as the complexity of the necessary diagnostics, clinical management should already be determined by an interdisciplinary tumor board at the time of initial diagnosis.     

An unusual case of diffuse Merkel cell carcinoma successfully treated with low dose radiotherapy

Merkel cell carcinoma (MCC) is a rare and highly aggressive neuroendocrine carcinoma of the skin. MCC should be included in the diagnosis of a rapidly growing infiltrating mass and histology as well as laboratory investigations such as Merkel cell polyoma virus (MCPyV) detection are valuable in its diagnosis. We present an unusual case of giant MCC‐positive MCPyV in a Greek woman located on the lower leg. Our patient is very unusual in terms of her extensive MCC and her rapid and complete response to radiotherapy.     

Metachronous Merkel cell carcinoma on both cheeks

Merkel cell carcinoma (MCC), an aggressive skin cancer with neuroendocrine features, has been found to be associated with a new type of human polyomavirus called Merkel cell polyomavirus (MCV). Patients diagnosed with MCC have a signi?cantly increased risk of a second primary cancer. We report here the first case of two primary MCCs arising on the face at different times, associated with MCV infection. The tumour on the patient's right cheek was surgically removed, followed by chemoradiation. After a 10-year tumour-free period, a new tumour developed on the patient's left cheek. Histological and immunohistochemical findings were consistent with MCC. The tumours had high MCV copy numbers and expressed large T antigen, which may play a major role in MCV-mediated carcinogenesis. This case highlights the close links between MCC and MCV.     

Expression of CXCR4, E-cadherin, Bcl-2, and survivin in merkel cell carcinoma: an immunohistochemical study using a tissue microarray

Merkel cell carcinoma (MCC) is a rare but highly aggressive cutaneous malignancy with a mortality rate exceeding that of melanoma. Although smaller studies of markers of progression have been performed, large-scale investigation has been difficult due to the rarity of this tumor. Investigation of 4 potential immunohistochemical progression markers using an MCC tissue microarray was performed. An immunohistochemical analysis of CXCR4, E-cadherin, Bcl-2, and Survivin was performed on a tissue microarray of two hundred twenty-seven 0.6-mm tumor cores-110 primary, 73 local/regional metastatic, and 44 distant metastatic-from 87 patients, 23 of which were sampled 2 or more times. There was a statistically significant increase in immunoreactivity to CXCR4 and Survivin in local/regional nodal MCC metastases compared with primary and distant metastatic lesions. No significant differences by disease location were found for either Bcl-2 or E-cadherin. These results suggest a potential role for CXCR4 and Survivin in MCC tumor progression. However, previous data from other studies suggesting a role for Bcl-2 and E-cadherin in MCC progression are not confirmed in this larger sample. Further discovery of additional markers are needed to better characterize this rare but deadly malignancy.     

Cutaneous mixed tumor, eccrine variant: a clinicopathologic and immunohistochemical study of 50 cases, with emphasis on unusual histopathologic features

Mixed tumor, eccrine type, is a rare cutaneous adnexal neoplasm, mostly reported as isolated case reports. A systematic analysis of its histopathologic and immunohistochemical features has not previously been performed on a large series. The purpose of our investigation was to study a large number of cutaneous eccrine mixed tumors so as to fully characterize the entire spectrum of changes in the epithelial and stromal components, with an emphasis on unusual histopathologic features that may represent a diagnostic pitfall. This article reports a light microscopic and immunohistochemical study of 50 cases of eccrine mixed tumor, complemented by a literature review. Our study identified some unusual histopathologic features, thus extending the morphologic spectrum of this neoplasm. These included prominent cribriform areas, clear cell change, pseudorosette structures, prominent osseous metaplasia, and physaliphorous-like cells. Most of these features have not been previously recorded in eccrine mixed tumors and may represent a potential diagnostic pitfall.     

A Case of Malignant Melanoma with Multiple Primary Lesions

Merkel cell carcinoma (MCC) is a small round cell tumor which does not characteristically stain with S‐100 protein. We report a case of an 83 year‐old male with a two‐month history of an ulcerated nodule on the right arm. Histopathology revealed small blue round cells arrayed in a trabecular pattern and in diffuse sheets, with scattered mitoses and necrosis. The cells were negative for vimentin, positive for NSE, focally positive for high molecular weight cytokeratins and diffusely positive for low molecular weight cytokeratins, including CK20. The findings were diagnostic of MCC, however, foci of S‐100 protein positive cells were also present in the tumor. Upon reviewing cases from Skin Pathology Laboratory at BUSM received between 1/1/2000 to 7/30/2004, we documented a total of 34 cases diagnosed as MCC; 24 were stained with S‐100 protein and this case was the only one that stained positively. S‐100 protein positivity of MCC, while having been previously reported, is an uncommon finding. We report our case to stress the importance of morphological and immunoperioxidase features for the diagnosis of Merkel cell carcinoma, particularly in the exceptional cases which exhibit S‐100 protein positivity.     

Combined intraepidermal neuroendocrine (Merkel cell) and squamous cell carcinoma in situ with CM2B4 negativity and p53 overexpression(*)

Primary cutaneous neuroendocrine carcinoma, also known as Merkel cell carcinoma (MCC), usually presents as a dermal and/or subcutaneous tumor. Rarely, it is confined to the epidermis or adnexal epithelium [MCC in situ (MCCIS)]. Little is known about the spectrum of features and biology of MCCIS. Herein, we report a case of MCCIS arising on the cheek of a 77-year-old Caucasian male, which was associated with squamous cell carcinoma in situ. The tumor cells of both the neuroendocrine and squamous components prominently involved adnexal structures but did not invade the dermis. The tumor cells with neuroendocrine features were immunoreactive for cytokeratin-20, chromogranin and synaptophysin. They also expressed p53 but were non-reactive with the monoclonal antibody CM2B4. Lack of labeling for CM2B4 is in keeping with prior observations of combined squamous and MCC. Our findings support the concept of a distinct subtype of virus-independent cutaneous neuroendocrine carcinoma that differs from conventional MCC. The observed overexpression of p53 suggests that the development of this tumor type may be related to chronic ultraviolet damage.     

Merkel cell carcinoma in situ

BACKGROUND: Merkel cell carcinoma (MCC) is a dermal small blue-cell tumor that occurs in the elderly on the sun damaged head and neck. Epidermal involvement is unusual and MCC limited to the epidermis is very rare. CASE REPORT: A slightly tender pink hyperkeratotic papule was noted on the dorsal right hand of a 76-year-old man with a history of multiple skin cancers. An intraepidermal proliferation of small blue cells distributed in nests and single units at all levels of the epidermis was found within a solar keratosis and adjacent to an area of squamous cell carcinoma in situ. Cytokeratin 20 and neuron specific enolase highlighted these cells and failed to reveal dermal involvement. There was no residue on re-excision. CONCLUSION: We report the third case of MCC in situ. These lesions have only been reported in association with squamous neoplasms on the extremities.     

Merkel cell carcinoma arising within a poroma: report of two cases

Merkel cell carcinoma (MCC) has been reported in association with other types of cutaneous neoplasms within the same lesion, including squamous cell carcinoma, Bowen's disease, actinic keratosis, follicular cysts, trichoblastoma and lentigo maligna, among others. However, the association of MCC and sweat gland tumors has never been described in the literature. We report two unique cases of MCC that developed within cutaneous poromas. A 56‐year‐old male (Patient 1) and an 81‐year‐old female (Patient 2) presented with nodules on the upper arm and lower back, respectively. Histopathologic study of both cases revealed a tumor in the dermis composed of poroid and cuticular cells intermingled with a proliferation of small round cells that showed characteristic histopathological and immunohistochemical features of MCC. In both cases, the two neoplasms were tightly admixed and distinct, suggesting that the MCC could have developed within a previously existing poroma. No morphological features of transition between the two tumors were seen. Neoplastic cells of MCC expressed immunoreactivity for chromogranin, synaptophysin, neuron‐specific enolase, CAM 5.2 and cytokeratin 20, the last two markers showing the characteristic paranuclear dot‐like pattern. In contrast, the poroma cells only expressed cytokeratin MNF116. Metastatic deposits were not identified in the regional lymph nodes or distantly.     

An unusual presentation of a congenital benign apocrine hamartoma

A case of an unusual benign apocrine hamartoma was studied by light microscopic, immunohistochemical, and electron microscopic methods. This tumor clinically showed a linear configuration and was located on the midline chest of a pubescent male. Microscopic studies revealed features of both a tubular apocrine adenoma and a syringocystadenoma papilliferum.