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Spitz claims in the book that “We’re Gonna Groove” on Coda was recorded in London in June 1969, seemingly sourcing the information from the album’s original liner notes. A typical finding of classic Spitz nevi are PAS+, eosinophilic, hyaline globules, so called Kamino bodies, located at the dermoepidermal junction With the better characterization of Spitz nevi as distinct melanocytic neoplasms, the first variant, the pigmented spindle cell nevus, was then recognized and described in 1975 ( 5). Subsequently, several more variants of SN, including the desmoplastic, pseudogranulomatous, and a variant with halo reaction were described in 1978 ( 6). Although combined nevi are commonly associated with blue nevi, combined SN is a relatively rare variant of combined nevi displaying populations of spitzoid melanocytes combined with one or more other distinct nevomelanocytes ( 152– 154). Typically, Combined SN are composed of either large epithelioid or spindle spitzoid melanocytes combined with either banal nevus, dysplastic nevus, or blue nevus cells ( 152– 154). Clinically, combined SN occur in patients of all ages and display a female predominance ( 152, 153). These lesions are small, symmetrical, and well-circumscribed ( 152).On early tours with Led Zeppelin, there were many sexual encounters with underage girls,” Spitz alleges. “No one gave a thought to whether these girls were well below the age of consent. Some were eighteen, some were sixteen, some were fourteen—mostly no one bothered to ask,” he alleges elsewhere. Junctional nests often show separation artifacts (clefting) to the surrounding epidermis and are oriented perpendicularly to the epidermis Concerning “Communication Breakdown,” Spitz writes that “the musicians sounded as if they weren’t in control of their instruments—a supernatural force had taken over and wired them directly into an atom smasher.” Spitz may not have had access to the three surviving Led Zeppelin band members, but his new interviews with associates including former Atlantic Records executive Phil Carson, Peter Grant’s former assistant Carole Brown, album cover designer Aubrey Powell and Plant’s PA Benji Le Fevre form a compelling narrative filled with recollections from people who were along for the ride as well. Spitz’s reassessment of groupie culture is likely to prove the book’s most divisive and headline-grabbing theme.
Translocated Spitz nevi. (A, B) Example of ALK fused Spitz nevus with a polypoid silhouette (A) and plexiform intersecting fascicles of fusiform melanocytes (B). (C, D) Example of ROS fused Spitz nevus with a diffuse proliferation of melanocytes (C) mostly in small nests (D). Spitz is fond of piling on the metaphors and similes to hammer home points to the reader. They often make the book more readable, but can grate on occasion. SM may exhibit similar dermoscopic features to SN, but in general tends to exhibit more asymmetry and more colors ( 34, 56). Compared to non-spitzoid melanoma, SM are less likely to exhibit a multicomponent dermoscopic pattern, atypical network, structureless areas, dark brown coloration and more likely to exhibit a pink Spitz-like pattern, red/pink and white coloration, shiny white areas, milky red areas, and polymorphous vascular patterns ( 34). Since Dr. Sophie Spitz’s initial description of “juvenile melanomas” in 1948, there has been a dramatic increase in the body of knowledge surrounding Spitz tumors. Although diagnosis of these lesions still heavily relies on clinical and histopathologic characteristics, the discovery of mutations and translocations associated with these lesions is reshaping the field, improving identification of these lesions. Decreased costs of useful ancillary studies such as NGS will improve accessibility to these tests and assist in the genetic diagnosis of Spitz tumors. Moving forward, these associations between morphology and genetic will help in better classification and will better inform the clinician not only in the potential behavior and prognosis of the lesion, but also, in case of a malignant diagnosis, in the identification of specific molecular targets for therapy. These histologic features have also inspired these lesions’ nomenclature which has evolved over time. There is indeed a relatively long list of synonyms, such as “spindle and epithelioid cell nevus”, “spindle-cell nevus”, “epithelioid cell nevus” and “nevus of large spindle and/or epithelioid cells”. The now most commonly used name of “Spitz Nevus” (SN) was established in 1967 by the Pathology Committee of the Queensland Melanoma Project, using an eponym honoring and marking the legacy of the late Dr. Spitz, prematurely passed away a decade earlier ( 4).
All the right details I’d want in harsh conditions are there too: a protective hood that moves with your head, glove-friendly zipper tabs, ventilation options across the front and under the arms. In the grandly titled “Led Zeppelin: The Biography,” due to be released on November 9, Spitz charts a comprehensive course through Led Zeppelin’s career, relying on more than 50 interviews with associates of the band to build up a well-told story of their success. The anaplastic lymphoma kinase (ALK) genes encode for a receptor tyrosine kinase in the insulin receptor family. First discovered in anaplastic large cell lymphoma (ALCL) as a driver translocation, ALK gene alterations have been described in several different tumors, including melanocytic neoplasms. ALK immunohistochemistry is a reliable and cost-effective marker that can be used to screen for potential translocation in this gene. Epithelioid morphology, high grade cytological atypia, multinucleated giant cells, p16 loss, junctional nests, desmoplasia ( 16, 23, 107) Gene fusion in NTRK1, 2 and 3 have been reported in a range of Spitz tumors. NTRK fusions were first reported in Spitz tumors by Wiesner et al, reporting gene rearrangement in NTRK1 in 16% of the 140 spitzoid lesions analyzed, including SN, AST and SM ( 13). In their paper the reported fusion partners were LMNA (most common) and TP53. NTRK1, a gene encoding for TRKA, is a particularly attractive target for cancer therapy, owing to its status as a critical protein in carcinogenesis ( 100). Activation of NTRK1 has been shown to play a role in cell signaling pathways such as PI3K/AKT and MAPK, affecting cell survival, proliferation, and regulated cell death ( 13). Morphologic analysis of NTRK1 fused Spitz neoplasms has revealed a small spindled cell morphology with Kamino bodies and frequent rosette formation. More recently, a filigree-like architectural pattern of the rete ridges has been described ( 100), as well as rosette-like features of dermal melanocytes, in Spitz tumors with NTRK1 fusion. A novel NTRK2-TFG gene fusion was reported last year in a nevus of Reed, identified through a screening with a pan-TRK immunohistochemistry antibody and confirmed through RNA sequencing ( 120).
Spitz clearly describes alleged acts, specifically accusing John Bonham of “attempted rape” of a flight attendant on a flight from Chicago to Los Angeles in 1975. In 2016, NTRK3 kinase fusions were added to the repertoire of kinase fusions found in Spitz melanoma and the effort to find additional molecular defects continue to this day, as an estimated 20-50% of Spitz tumors remain with no known genetic mutations ( 14, 15). Most recently, MAP3K8 translocations have been identified as an additional genetic driver ( 16, 17). Other authors have exclusively studied pediatric populations. In a series of 512 SN and 107 AST in this younger population, the median ages for each were 7.4 and 7.2, respectively ( 33). Though data is limited due to the relatively rare nature of SM in a pediatric population, the mean age tends to be higher at 12.9 years ( 34).
Spitz neoplasms
Melan-A, SOX10 and S100 tend to display identical staining patterns in melanocytic lesions, including SN ( 86). Subtypes of the family of S100 proteins may be of some help in distinguish different melanocytic lesions; in a study of 42 SN cases, all of these lesions strongly expressed the S100A6 protein compared with only 33% of 105 melanoma cases ( 72). Moreover, SN may display a diffuse pattern of S100A6 whereas melanoma appears to display a patchy distribution ( 21, 72). Another marker, MITF, appears to have a somewhat lower intensity in SN ( 18, 87, 88). In recent years, he appears to have relaxed this position, publishing an official photographic history of the band for its fiftieth anniversary in 2018 and co-operating with an authorised documentary film set to be released next year.
Following the discovery of BRAF mutations in cancers, including melanoma, it was found that benign Spitz nevi do not contain actually BRAF mutations, marking an important distinction of these tumors with other melanocytic lesions ( 10– 12). More recently, Wiesner and colleagues found that kinase fusions and translocations are commonly found across the spectrum of Spitz neoplasms ( 13). In-frame kinase fusions and translocations of ROS1, NTRK1, ALK, BRAF, and RET were described, and will be described later in this review ( 13). Despite attempts to clinically characterize Spitz lesions, these lesions share many clinical characteristics, such as size, location, and color, with other skin lesions, leading to a wide differential. Spitz lesions, in particular AST and SM, can present very similarly to melanoma on physical exam, particularly with asymmetry, diameter >6mm, and color variegation along with dark brown coloration ( 29, 31, 34, 45). Other melanocytic lesions are also high on the differential for Spitz lesions and include congenital melanocytic nevus, atypical nevus, blue nevus, and Clark nevus ( 29, 31, 36, 37, 46). There were few sounds more memorable than John Paul’s walking bass that lumbered along ominously like Lenny in Of Mice and Men,” Spitz writes about “Dazed And Confused.” Gl.inet uses a custom skin, so if you're familiar with OpenWRT, what you get with the Spitz will be slightly different. All the features are there—and you can install anything extra you want—but things might be in slightly different places than you're used to.Robert Plant sings on “Ramble On” that “mine’s a tale that can’t be told,” but over the years many authors have attempted to tell the story of Led Zeppelin, with varying levels of success. The book’s notes reference just four bootleg recordings that Spitz relied upon. His preference is to quote newspaper articles to reproduce their impressions of each show.
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