Immunosuppression
The incidence of MCC is increased in conditions with defective immune functions such as malignancy, HIV infection, and organ transplant patients, etc. Conversely, patients with brisk immune response have been shown to have improved prognoses. This is suspected to be due to the inability of the body to defend itself from infection by or reactivation of MVC. The body of data indicating the importance of immune function in MCC pathogenesis has been exploited for the development of immunotherapies discussed below. Diagnosis
Diagnosis of MCC begins with a clinical examination of the skin and lymph nodes. Following clinical exam, definitive diagnosis of Merkel cell carcinoma (MCC) requires examination of biopsy tissue to identify its histopathologic features. An ideal biopsy specimen is either a punch biopsy or a full-thickness incisional biopsy of the skin including full-thickness dermis and subcutaneous fat. On light microscopy, MCC shows basaloid tumor nests with neuroendocrine features ("salt and pepper" chromatin, scarce cytoplasm, and brisk mitotic activity). In addition to standard examination under light microscopy, immunohistochemistry (IHC) is also generally required to differentiate MCC from other morphologically similar tumors such as small cell lung cancer, the small cell variant of melanoma, various cutaneous leukemic/lymphoid neoplasms, and Ewings sarcoma. Neuroendocrine molecular markers such as synaptophysin or chromogranin A are characteristic of MCC and other neuroendocrine tumors, while other markers such as PAX5 or cytokeratin 20 can distinguish MCC from these tumors. Longitudinal imaging may also help in ruling out a diagnosis of metastatic small cell lung cancer.
All pathways culminate in the production of a C3 convertase, which catalyses C3 into its constitutive parts (better detailed here – classical complement pathway).In brief, the crucial role of C1q in the pathway is its importance as the first protein to start the complement cascade (which ends in the destruction of the invading bacteria or virus), and its ability to link the two important arms of the immune system – the innate immune system: a broad defence system; and the adaptive immune system: the strong immune response capable of remembering previous infections, allowing fast response against recurrent infections, meaning that people with a normal immune system dont continually catch the same cold or same strain of flu repeatedly.Case studies of individuals with HUV have also highlighted other potential complicating factors which it seems the anti-C1q antibodies play a role in. This can mean in some cases the deposition of large immune complexes in the kidney which cannot be cleared by the usual cells of the immune system (e.g. macrophages which are unable to bind the Fc portion of the C1q antibody), leading to further complications. This seems to be rare, but can occur when a pre-existing renal condition is apparent. Also, there has been some speculation as to an additional autoantibody against an inhibitor protein (in the complement pathway) named C1-inhibitor. The inhibition of C1-inhibitor leads to over-activation of the complement pathway and one protein that builds up controls angioedema (vessel – swelling), resulting in excess water building up under the skin (the weal appearance).