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An introduction to skin and skin disease
Published in Rashmi Sarkar, Anupam Das, Sumit Sethi, Concise Dermatology, 2021
These are slow-adapting mechanoreceptors located in the basal layer of the epidermis. They are found in digits, lips, oral cavity, and hair follicles. They have important clinical bearing because of the association with the development of Merkel cell carcinoma and neuroendocrine carcinoma.
Comparative Anatomy, Physiology, and Biochemistry of Mammalian Skin
Published in David W. Hobson, Dermal and Ocular Toxicology, 2020
The haarscheibe is an elevated touch receptor found in mammalian skin. Among various species, they are structurally similar although they may differ in size, spacing, and the degree of elevation above the surrounding epithelium. A typical haarscheibe contains 25 Merkel cells.119 In the cat and rat the haarscheibe can easily be seen with the naked eye, especially after depilation. In man a haarscheibe is difficult to identify with the unaided eye. When found, they seem to be abundant on the neck and abdomen.115 When viewed under a dissecting microscope, they look like shiny domes and are more translucent than the surrounding epithelium.119 Within the haarscheibe, tufts of blood vessels can occasionally be seen and these give it an erectile quality. The haarscheibe is more resistant to pressure than the surrounding dermis because it has a “denser dermal core and two layers of fibril containing pseudostratified columnar epithelium”.115 In rats they are 100 to 300 μm in diameter and 3 to 5 mm apart. In mice, rats, guinea pigs, and chinchillas, they appear to be associated with tylotrich hairs.120 Their epithelium contains large basal keratinocytes which have a columnar orientation. Merkel cells are located in the basal layer of their epidermis.
Benign Lymph Node Lesions
Published in Harold R. Schumacher, William A. Rock, Sanford A. Stass, Handbook of Hematologic Pathology, 2019
Once the diagnosis of Merkel cell carcinoma was established, it was recommended to thoroughly evaluate the patient for evidence of a primary lesion in the skin. In this case, no lesion was identified. The diagnosis of metastatic Merkel cell carcinoma in a lymph node in the absence of an identifiable primary lesion in the skin is extremely rare and always difficult to explain, but there have been sporadic reports and case presentations of such occurrences. One report included eight patients with Merkel cell carcinoma with involvement of the inguinal lymph nodes (five cases), axillary lymph nodes (two cases), and submandibular lymph nodes (one case) in which no primary skin lesion was found. In all these cases, the patients underwent extensive evaluation, and rigid criteria were followed in making the diagnosis of Merkel cell carcinoma (2).
Tumor mutational burden as a tissue-agnostic biomarker for cancer immunotherapy
Published in Expert Review of Clinical Pharmacology, 2021
Winnie W. Y. Sung, James C. H. Chow, William C. S. Cho
Results above suggest that the benefit of immunotherapy for TMB-high versus non-TMB-high tumors vary across tumor types. In an analysis to evaluate the relationship between TMB and ORR across multiple tumor types, Yarchoan et al observed a significant correlation between TMB and ORR, yet different tumor types respond better or worse than predicted by TMB[1]. This variation in tumor immunogenicity may be explained by other immune-related mechanisms not captured by TMB, such as viral antigen expression and antigen presentation efficiency[5]. For example, the presentation of viral antigens may confer a higher immunogenic response in Merkel cell carcinoma[6]. In contrast to MSI-H/dMMR status, TMB is a continuous quantitative biomarker. Thus, it is important to determine the pertinent threshold for defining TMB-H and whether that threshold is the same across tumor types.
Nanocrystal: a novel approach to overcome skin barriers for improved topical drug delivery
Published in Expert Opinion on Drug Delivery, 2018
Viral Patel, Om Prakash Sharma, Tejal Mehta
Apart from keratinocytes, melanocytes, Langerhans, and Merkel cells are also present in the epidermis. Melanocytes are the cells that have a potential to secrete a pigment known as melanin. They originate from the neural crest and are dopa-positive cells. Melanin is stored in the special cell organelle known as melanosome and is transported by structures called dendrites to keratinocytes [36]. Similar to the melanocytes, few cells are also present which lack pigment secretion and are dopa negative, known as the Langerhans cells. They were first identified, by a scientist named Langerhans, by staining the human epidermis with gold chloride [37]. This epidermal Langerhans cells originate in the bone marrow and migrate toward the skin epidermis via blood vessel walls of the dermis [38]. In epidermis, the Langerhans cells perform the function of antigen-presenting cells. They uptake the antigens from the skin and migrate toward the regional lymph nodes and activate the T cells, which help in fighting the skin infections. Merkel cells are positioned on the basal epidermal layer in touch-sensitive areas; thus, they are also called as touch cells or Tastzellen [39,39].
Avelumab: a new standard for treating metastatic Merkel cell carcinoma
Published in Expert Review of Anticancer Therapy, 2018
Mairead Baker, Lisa Cordes, Isaac Brownell
Merkel cell carcinoma is a rare and aggressive neuroendocrine skin cancer that more commonly affects sun-exposed fair skin, immunocompromised patients, and the elderly. The mean age at diagnosis is 75 and approximately 37% of patients have nodal disease at presentation whereas 5–12% present with metastatic disease [1–4]. In patients with metastatic disease, the 5-year survival rate is estimated to be 0–18% [3,5]. MCC is the second leading cause of skin cancer deaths and, per case, is twice as lethal as melanoma, with a relative mortality between 33% and 46% [4,6,7]. First described in 1972, worldwide incidence and mortality from MCC has risen dramatically over the past few decades, and MCC annual incidence is now estimated to be 0.2, 0.7, and 1.6 cases per 100,000 people in Europe, the USA, and Australia, respectively [4,8–10].