large breasts

Anaplastic large cell lymphoma (ALCL) refers to a group of non-Hodgkin lymphomas in which aberrant T cells proliferate uncontrollably. Considered as a single entity, ALCL is the most common type of peripheral lymphoma and represents ~10% of all peripheral lymphomas in children. The incidence of ALCL is estimated to be 0.25 cases per 100,000 people in the United States of America. There are four distinct types of anaplastic large cell lymphomas that on microscopic examination share certain key histopathological features and tumor marker proteins. However, the four types have very different clinical presentations, gene abnormalities, prognoses, and/or treatments.ALCL is defined based on microscopic histopathological examination of involved tissues which shows the presence of at least some ALCL-defining pleomorphic cells. These "hallmark" cells have abnormal kidney-shaped or horseshoe-shaped nuclei, prominent Golgi, and express the CD30 tumor marker protein on their surface membranes. In 2016, the World Health Organization (WHO) separated ALCL into four types: ALK-positive ALCL (also termed ALK+ ALCL), ALK-negative ALCL (ALK− ALCL), primary cutaneous ALCL (pcALCL), and breast implant-associated ALCL (BIA-ALCL). WHO defined BIA-ALCL as an ALCL type provisionally, i.e. subject to redefinition if future studies should support such a change.ALK-positive and ALK-negative ALCL are aggressive systemic lymphomas. They are differentiated based on their expression of an abnormal ALK protein made by a somatic recombination in the ALK gene. ALK, i.e. anaplastic lymphoma kinase, is a protein product of the ALK gene located on chromosome 2. In ALK-positive ALCL, a portion of the ALK gene has merged with another site on the same or different chromosome to form a chimeric gene consisting of part of the new site and part of the ALK gene coding for ALK's activity. This chimeric gene overproduces a fusion protein with excessive ALK activity. ALK is a serine/threonine-specific protein kinase that activities PI3K/AKT/mTOR, Ras-activated ERKs, Janus kinase-activated STAT proteins, and other cell signaling pathways as well as the expression of various genes by epigenetic mechanisms. Activations of these signaling pathways and genes may stimulate cell growth, proliferation, survival, and/or other behaviors that promote malignancy. ALK-negative ALCL, while not involving ALK translocations, has, in a variable percentage of cases, various translocations, rearrangements, and mutations that may contribute to its development.pcALCL and BIA-ALCL are far less aggressive lymphomas that tend to be localized to one or a very few sites. pcALCL presents as a single or, less commonly, multifocal skin papules or tumors that typically are limited to the dermis without infiltrating to the subcutaneous tissues or spreading to other sites. Its neoplastic cells may contain some gene translocations including, in very rare cases, ones with the ALK gene that are similar to those in ALK-positive ALCL. BIA-ALCL is caused by and develops around a breast implant. It typically presents many years after the surgical implantation as a deformation, textural change, and/or pain emanating in the area around implanted breast. In most cases, the disease is localized to the involved breast. BPI-ALCL is associated with occasional mutations in one or two genes but has not been reported to be associated with products of gene translocations or rearrangements.

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