Thermal keratoses and squamous cell carcinoma in situ associated with erythema ab igne

A 60-year-old black woman had a large hyperkeratotic lesion and multiple smaller hyperkeratotic papules and plaques on the lower part of her legs in areas of erythema ab igne. Histologic examination of the largest lesion showed hyperplastic carcinoma in situ and the multiple smaller lesions showed varying degrees of squamous cell atypia and dermal elastosis. Histologically, these lesions were identical to solar-induced atypia, indicating that squamous cell carcinoma arising in erythema ab igne may be biologically similar to actinic carcinoma. Discussed here are clinical and histologic features of the thermal-induced lesions and other types of thermal-induced carcinomas.     

Merkel cell carcinoma

Merkel cell carcinoma (cutaneous neuroendocrine carcinoma) is an uncommon, highly malignant, neuroendocrine skin tumour. Typically, the primary is a fast-growing tough dermal nodule that is characterized histologically by uniform round cells with a small cytoplasmic rim. The tumour cells express the cytokeratins 8, 18, 19, 20, neurofilament, synaptophysin, chromogranin, and neuron-specific enolase. A high frequency of local recurrences (25-77%) and lymph-node metastases (50%) are characteristic features of Merkel cell carcinoma. The 5-year survival rate is 30-74%. Merkel cell carcinomas are highly radiosensitive. Thus, besides surgical methods, radiation should be included into the treatment concept in every stage. We present four cases of Merkel cell carcinoma with different courses for a review-like discussion of this disease giving instructions for rapid diagnosis and effective therapy.     

Squamous cell carcinoma developing in thermal keratosis

Two cases of squamous cell carcinoma (SCC), both of them developed from thermal keratosis arising in areas of erythema ab igne (EAI) are reported. The lesions were located on the legs of two elderly Japanese women who had histories of chronic exposure to heat from a “kotatsu”, a type of leg-warmer widely used in Japan. In one case, metastasis to regional lymph nodes occurred. It is emphasized that keratotic lesions arising in an area of EAI should be excised or biopsied because of the possibility of metastasizing SCC developing from them.     

Merkel cell carcinoma with squamous and sarcomatous differentiation

Merkel cell carcinoma is an aggressive neuroendocrine tumor historically thought to arise from neural crest-derived cutaneous neuroendocrine cells. Recent evidence supports an epidermal origin. We present a case of Merkel cell carcinoma arising on the upper arm of a 94-year-old woman that had multiple morphologic patterns: small cells typical of Merkel cell carcinoma, malignant cells with squamous differentiation and malignant poorly differentiated spindle cells. Subsequent metastatic disease in regional lymph nodes showed only the small cells and the malignant spindle cells. To our knowledge, this is the first case of Merkel cell carcinoma showing these three patterns of differentiation at first presentation. This morphology raises the possibility that Merkel cell carcinomas may arise from epidermal stem cells that can differentiate along different lines.     

Merkel细胞癌合并原位鳞状细胞癌一例并文献复习

Merkel细胞癌是一种罕见的、具有高度侵袭性的皮肤神经内分泌癌,好发于老年人的日光暴露部位,尤其是头颈部(41%～50%),其次是四肢(32%～38%)。Merkel细胞癌可与鳞状细胞癌、鲍温病、基底细胞癌等皮肤肿瘤合并发生。我们报道一例发生在非光暴露部位的Merkel细胞癌合并原位鳞状细胞癌,并对相关文献进行复习。     

Two cases of squamous cell carcinoma arising from erythema ab igne

This report describes two female patients, 69 and 79 years old, with squamous cell carcinoma (SCC) developing from erythema ab igne (EAI) due to thermal irradiation from a sunken hearth (irori in Japanese) or an underfloor brazier covered with a quilt (kotatsu in Japanese). EAI on the knees and lower thighs showed reticular pigmentation at its periphery and poikiloderma in the center with many keratotic nodules. In both cases, the SCCs were located almost symmetrically on an anterior site 1/3 of the way down both lower thighs. They were surrounded by many keratotic nodules. Histologically, these nodules showed an atypia of the epidermal cells, indicating carcinoma in situ resembling actinic keratosis ro Bowen's disease. It was also strongly suggested that the SCCs in these patients had developed from the keratotic nodules. EAI appeared to have played a pathogenetic role in the cutaneous carcinoma.     

Merkel cell carcinoma: epidemiology,clinical features,diagnosis and treatment of a rare disease

Merkel cell carcinoma is a rare skin cancer with neuroendocrine differentiation. The risk factors include sun exposure, advanced age, immunosuppression (such as transplant recipients, patients with lymphoproliferative neoplasms, or patients with HIV), and Merkel cell polyomavirus infection. Clinically, Merkel cell carcinoma appears as a cutaneous or subcutaneous plaque or nodule, but this tumor diagnosis is rarely made clinically. Therefore, histopathology and immunohistochemistry are usually necessary. Primary tumors without evidence of metastases are treated with complete surgical excision and appropriate surgical margins. The presence of occult metastasis in a lymph node is frequent and a sentinel lymph node biopsy should be performed. Postoperative adjuvant radiotherapy increases local tumor control. Recently, agents that block the PD-1/PD-L1 pathway have shown objective and durable tumor regression in patients with advanced solid malignancies. The first anti-PD-L1 antibody used in patients with Merkel cell carcinoma was avelumab, but pembrolizumab and nivolumab have also shown efficacy. This article describes the current state of knowledge of the epidemiology, diagnosis, and staging of Merkel cell carcinoma, as well as new strategies for its systemic treatment.     

Merkel cell carcinoma update: the case for two tumours

Merkel cell carcinoma (MCC) is an aggressive tumour with neuroendocrine differentiation. Clinically significant differences within the entity we know as MCC are apparent. This review aims to evaluate the evidence for differences in tumours within Merkel cell carcinoma and to stratify these. A literature search of research pertaining to various characteristics MCC was undertaken from 1972, when Merkel cell carcinoma was first described, to 2018, using PubMed and similar search engines. A total of 41 papers were analysed, including clinical trials, laboratory-based research and reviews. A proportion of MCC has Merkel cell polyomavirus genome integrated (MCPyV+) while others do not (MCPyV−). Both types have a different mutation burden. MCPyV+ tumours are likely true neuroendocrine carcinomas, with a dermal origin, probably from fibroblasts which have been transformed by integration of the viral genome. MCPyV−tumours are likely derived from either keratinocytes or epidermal stem cells, are probably squamous cell carcinomas with neuroendocrine differentiation, and are related to sun damage. Prognostic factors (apart from tumour stage) include the MCPyV status, with MCPyV+ tumours having a better prognosis. P63 expression confers a worse prognosis in most studies. CD8+ lymphocytes play an important role, providing a possible target for PD1/PD-L1 blockade treatment. The incidence of MCC varies from country to country. Countries such as Australia have a high rate and a far greater proportion of MCPyV− tumours than places such as the United Kingdom. MCC doubtlessly encompasses two tumours. The two tumours have demonstrated differences in prognosis and management. One is a neuroendocrine carcinoma related to MCPyV integration likely derived from fibroblasts, and the other is a UV-related squamous cell carcinoma with neuroendocrine differentiation, presumptively derived from either keratinocytes or epidermal stem cells. We propose naming the former Merkel type sarcoma and the latter squamous cell carcinoma, Merkel type.     

Secondary neuroendocrine carcinomas of the skin. An immunohistochemical comparison with primary neuroendocrine carcinoma of the skin ("Merkel cell" carcinoma)

Since the initial clinical presentation of visceral neuroendocrine carcinoma is occasionally a cutaneous metastasis, diagnostic confusion with primary neuroendocrine carcinoma of the skin (Merkel cell carcinoma) may ensue. In this study, seven cases of secondary cutaneous neuroendocrine carcinoma were immunohistochemically compared with twenty-one Merkel cell carcinomas for ten antigenic moieties that have been associated with endocrine tumors. Six of seven secondary tumors stained for bombesin, leucine enkephalin, methionine enkephalin, or beta-endorphin, none of which was detected in the primary cutaneous neuroendocrine carcinomas. These data suggest that immunohistochemical study may be useful in separating primary from secondary neuroendocrine tumors of the skin and may assist in directing clinical attention to the most probable site of visceral neoplasia.     

Cytokeratin 20: a marker for diagnosing Merkel cell carcinoma

Merkel cell carcinoma is an aggressive cutaneous neoplasm that is often difficult to diagnose because of its histologic and immunohistochemical similarity to metastatic oat cell carcinomas and other cutaneous neoplasms. Our purpose was to determine the utility of immunoperoxidase staining of cytokeratin 20 (CK 20), a newly discovered intermediate filament protein, in Merkel cell carcinomas and other cutaneous tumors. Sixty-one tumors were sectioned and stained with antibodies directed at CK 20. The staining of Merkel cell carcinomas was compared with metastatic oat cell carcinomas, lymphomas, squamous cell carcinomas, basal cell carcinomas, melanomas, metastatic carcinoids, spiradenomas, eccrine carcinomas, adenoidcystic carcinoma, sebaceous carcinomas, hidradenomas, sebaceous epitheliomas, trichoblastomas, mixed tumors, and metastatic adenocarcinomas. Nine of 10 Merkel cell carcinomas stained with antibody to CK 20. Two metastatic carcinomas to the skin were also positive. One hidradenoma and one squamous carcinoma exhibited focal staining, but were otherwise negative. All other tumors were nonstaining. Cytokeratin 20 is a sensitive and specific marker for Merkel cell carcinoma and is helpful in distinguishing between Merkel cell carcinoma and other malignant and benign neoplasms.     

Bcl-2 antisense oligonucleotides (G3139) inhibit Merkel cell carcinoma growth in SCID mice

Merkel cell carcinoma was first described in 1972 by Toker and is an aggressive neuroendocrine skin tumor with a high metastatic potential. Merkel cell carcinoma is thought to derive from the neuroendocrine (Merkel) cells of the skin, although in contrast to fetal and especially adult Merkel cells, Merkel cell carcinomas express high levels of the Bcl-2 oncoprotein. Bcl-2 is capable of blocking programmed cell death and has been shown to play an important role in normal cell turnover, tumor biology, and chemoresistance. High Bcl-2 expression leading to prolonged survival of cells may therefore be of importance in the biological and clinical characteristics of Merkel cell carcinoma. In a SCID mouse xenotransplantation model for human Merkel cell carcinoma, we investigated the influence of the bcl-2 antisense oligonucleotide G3139 (Genta) on tumor growth in comparison with control oligonucleotides or cisplatin. Bcl-2 antisense treatment, targeting the first six codons of the bcl-2 mRNA, resulted in either a dramatic reduction of tumor growth or complete remission, whereas reverse sequence and two-base mismatch control oligonucleotides or cisplatin had no significant antitumor effects compared with saline-treated controls. Apoptosis was enhanced 2.4-fold in the bcl-2 antisense treated tumors compared with the saline-treated group, and no other treatment showed a comparable increase in apoptosis. Our findings suggest that bcl-2 antisense treatment may be a novel approach to improve treatment outcome of human Merkel cell carcinoma.     

Unusual cutaneous carcinoma with features of small cell (oat cell-like) and squamous cell carcinomas. A variant of malignant Merkel cell neoplasm

Three unusual primary neoplasms in the skin that occurred in elderly patients (64, 77, and 69 years of age) are presented. Two histologic components were found in each of the three neoplasms, one being small cell or oat cell-like carcinoma and the other squamous cell carcinoma. Study by electron microscopy revealed neurosecretory granules, though few, in the small cell component. The lack of clinical evidence of oat cell carcinoma elsewhere, the autopsy finding of two histologic components in one patient, and the findings by conventional and electron microscopy lead us to conclude that these three neoplasms are primary in the skin and of Merkel cell origin. We suggest further that small cell carcinoma of the skin represents a poorly differentiated counterpart of trabecular carcinoma. The spectrum of malignant Merkel cell neoplasm is, therefore, expanding. Two of our three patients died of their neoplasms 2 and 2 1/2 years, respectively, after the initial diagnosis.     

Bullous erythema ab igne

Erythema ab igne is a localized, cutaneous condition, consisting of reticulate hyperpigmentation, dusky erythema, epidermal atrophy, and telangiectasia, all the result of repeated exposures to heat. We describe a patient with a bullous form of erythema ab igne: bullae and crusts within a localized area of reticular, brown, macular pigmentation on the lateral side of the left leg, an area that had repeated close exposure to an electrical heater over the previous 3 months. We believe that bullous erythema ab igne, something rarely reported in the literature, should be considered a well-defined variant of erythema ab igne; it may be more common than the literature suggests.     

Primary cutaneous neuroendocrine carcinoma (Merkel cell tumor). An adnexal epithelial neoplasm

We report 18 cases of primary cutaneous neuroendocrine carcinoma (CNEC, Merkel cell tumor) that occurred mainly in the sun-exposed skin of elderly patients as dermal and subcutaneous masses of generally monomorphic cells with foci of pronounced pleomorphism. All 18 cases showed immunoreactivity for neuron-specific enolase (NSE), whereas 16 of them showed immunoreactivity for another neuroendocrine marker, protein gene product 9.5 (PGP 9.5). Positivity for PGP 9.5 was more intense and more sharply localized to tumor cells than the staining for NSE. Immunoreactivity for keratins detected by AE1/AE3 and CAM 5.2 monoclonal antibodies was found in 16 and 15 cases, respectively, with prominent paranuclear globular staining. One case stained positively for S-100 protein; all were negative for leukocyte common antigen (LCA). Typical ultrastructural features of neuroendocrine differentiation were noted in all of 14 tumors examined. Morphological and immunohistochemical similarities between these neoplasms and pulmonary small-cell anaplastic carcinoma, now thought to be of bronchial basal cell origin, suggest that CNEC are also derived from epithelium. In addition, their dermal location suggests that this epithelium is likely to be adnexal rather than epidermal.     

Laptop induced erythema ab igne

Erythema ab igne is a reticular, pigmented dermatosis caused by prolonged and repeated exposure to infrared radiation that is insufficient to produce a burn. The use of laptop computers has increased manifold in the recent past. Prolonged contact of the laptop with the skin can lead to the development of erythema ab igne. We present a case of erythema ab igne secondary to laptop use in an Indian student.     

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.     

Postoperative hyponatremia in a patient with ACTH-producing Merkel cell carcinoma

Merkel cell carcinoma is characterized by specific neuroendocrine features and the expression of several neuropeptides. We report a case of Merkel cell carcinoma with post-surgical hyponatremia in an 85-year-old Japanese woman. A tumor on the left cheek histopathologically showed the characteristics of Merkel cell carcinoma together with Bowen's disease. Although an increased level of ACTH was found both in the tumor and in the peripheral blood, the postoperative hyponatremia in our patient seems more likely to have been caused by the stress of the operation and indapamide, considering that the ACTH level in the tumor was much lower than those in other ectopic ACTH-producing tumors in previous reports.