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• W3044804760 abstract "Editorial note: Welcome to the Journal of Investigative Dermatology (JID) Cells to Surgery Quiz. In this monthly online-only quiz, the first question (“What is your diagnosis?”) relates to the clinical image shown, while additional questions concern the findings reported in the JID article by Quan et al., 2020Quan V.L. Zhang B. Zhang Y. Mohan L.S. Shi K. Wagner A. et al.Integrating next-generation sequencing with morphology improves prognostic and biologic classification of Spitz neoplasms.J Invest Dermatol. 2020; 140: 1599-1608Abstract Full Text Full Text PDF Scopus (23) Google Scholar (https://doi.org/10.1016/j.jid.2019.12.031). Detailed answers and a list of relevant references are available following the Quiz Questions below. 1.What is your diagnosis?a.Atypical Spitz nevusb.Melanomac.Melanocytic nevusd.Infantile hemangiomae.Benign fibrous histiocytoma2.What is false about the management and/or prognosis of atypical Spitz tumors (ASTs)?a.The diameter of the lesion should be considered in risk stratification of pediatric AST.b.Patients with histopathologically diagnosed ASTs should undergo excision with clear margins regardless of age.c.Sentinel lymph node biopsy improves the prognosis for patients with AST.d.Patients with ASTs with sentinel lymph node involvement have better outcomes than patients with similar-staged conventional melanoma.e.The presence of TERT-p mutations is a predictor of recurrence.3.Quan et al., 2020Quan V.L. Zhang B. Zhang Y. Mohan L.S. Shi K. Wagner A. et al.Integrating next-generation sequencing with morphology improves prognostic and biologic classification of Spitz neoplasms.J Invest Dermatol. 2020; 140: 1599-1608Abstract Full Text Full Text PDF Scopus (23) Google Scholar performed DNA and RNA sequencing on 80 Spitz tumors (STs), 26 Spitz melanomas (SMs), and 22 melanomas with Spitzoid features (MSFs) to characterize the genomics of Spitz neoplasms and assess whether the integration of genomic data with morphological diagnosis improves classification and prognostication. All of the following are consistent with their findings, except:a.The ST group had a kinase fusion as the primary initiating genomic event in 73% of cases.b.Two new fusions, MYO5A-FGFR1 and MYO5A-ERBB4, are found in the ST group.c.Kinase fusions are detected in the MSF group.d.Classification incorporating genomic data was highly predictive of recurrence.e.The classification and ability to predict the behavior of Spitz neoplasms can be improved by incorporating genomic data. See following pages for detailed answers. 1.What is your diagnosis?CORRECT ANSWER: a. Atypical Spitz nevusSpitz tumors (STs) are uncommon melanocytic tumors characterized by their composition of epithelioid and/or spindled cells. The clinical and histological classification of Spitz-type tumors is complex and encompasses a spectrum of lesions ranging from benign or low-grade lesions to malignant lesions. Based on clinical, histopathologic, and genetic characteristics, lesions can be categorized into three provisional groups from benign to malignant: common Spitz nevus (CSN), atypical Spitz tumor (AST), and Spitz melanoma (SM) (Luo et al., 2011Luo S. Sepehr A. Tsao H. Spitz nevi and other Spitzoid lesions part I. Background and diagnoses.J Am Acad Dermatol. 2011; 65: 1073-1084Abstract Full Text Full Text PDF PubMed Scopus (67) Google Scholar). Of the three, AST is the most challenging to diagnose and treat, as it has intermediary features that significantly overlap with both its more benign and malignant counterparts. Figure 1 shows an atypical Spitz nevus (AST).Atypical Spitz nevi typically occur between the first and second decades of life, although there is overlap in age distribution with both CSN and SM (Crotty et al., 2002Crotty K.A. Scolyer R.A. Li L. Palmer A.A. Wang L. McCarthy S.W. Spitz naevus versus Spitzoid melanoma: when and how can they be distinguished?.Pathology. 2002; 34: 6-12Abstract Full Text PDF PubMed Scopus (99) Google Scholar). Clinically, ASTs are irregularly pigmented, nodular lesions that occur classically on the back (Luo et al., 2011Luo S. Sepehr A. Tsao H. Spitz nevi and other Spitzoid lesions part I. Background and diagnoses.J Am Acad Dermatol. 2011; 65: 1073-1084Abstract Full Text Full Text PDF PubMed Scopus (67) Google Scholar). These tumors are generally more pigmented than CSNs, which are often pink to flesh-colored because of their low levels of melanin and increased vascularity (Luo et al., 2011Luo S. Sepehr A. Tsao H. Spitz nevi and other Spitzoid lesions part I. Background and diagnoses.J Am Acad Dermatol. 2011; 65: 1073-1084Abstract Full Text Full Text PDF PubMed Scopus (67) Google Scholar). However, approximately 10% of CSNs are pigmented, and colors range from tan, brown, to even black, making distinction from ASTs challenging (Lyon, 2010Lyon V.B. The Spitz nevus: review and update.Clin Plast Surg. 2010; 37: 21-33Abstract Full Text Full Text PDF PubMed Scopus (24) Google Scholar). ASTs are typically >1 cm in diameter and present with some irregularity and ulceration on the surface compared with CSNs and are more likely to be elevated (nodular) compared with SM (Luo et al., 2011Luo S. Sepehr A. Tsao H. Spitz nevi and other Spitzoid lesions part I. Background and diagnoses.J Am Acad Dermatol. 2011; 65: 1073-1084Abstract Full Text Full Text PDF PubMed Scopus (67) Google Scholar). The surface of a CSN is often smooth with sharply demarcated borders, and deviation from these typical characteristics is suggestive of AST. On dermoscopy, AST fails to present a specific clinical pattern and often resembles melanoma and sometimes dermatofibroma (Luo et al., 2011Luo S. Sepehr A. Tsao H. Spitz nevi and other Spitzoid lesions part I. Background and diagnoses.J Am Acad Dermatol. 2011; 65: 1073-1084Abstract Full Text Full Text PDF PubMed Scopus (67) Google Scholar). On histopathology, AST is characterized by infiltrative organization, poorly circumscribed borders, lack of Kamino bodies, subcutaneous involvement, and disrupted and ulcerated epidermis (Luo et al., 2011Luo S. Sepehr A. Tsao H. Spitz nevi and other Spitzoid lesions part I. Background and diagnoses.J Am Acad Dermatol. 2011; 65: 1073-1084Abstract Full Text Full Text PDF PubMed Scopus (67) Google Scholar). Presence of Kamino bodies, maturation, junctional clefting, and uniformity are good indicators of a benign Spitz nevus as opposed to AST (Crotty et al., 2002Crotty K.A. Scolyer R.A. Li L. Palmer A.A. Wang L. McCarthy S.W. Spitz naevus versus Spitzoid melanoma: when and how can they be distinguished?.Pathology. 2002; 34: 6-12Abstract Full Text PDF PubMed Scopus (99) Google Scholar). AST is also associated with mitoses ≥2–6 per mm2, more heterogeneous cell types in addition to spindled or epithelioid cells, and a high nuclear to cytoplasmic ratio, although SM can present with similar features (Kamino, 2009Kamino H. Spitzoid melanoma.Clin Dermatol. 2009; 27: 545-555Abstract Full Text Full Text PDF PubMed Scopus (39) Google Scholar).Diagnosis using clinical, dermoscopic, and even histological features is still far from straightforward. Spitzoid melanomas are thought to have their own set of defining characteristics (Lallas et al., 2017aLallas A. Apalla Z. Ioannides D. Lazaridou E. Kyrgidis A. Broganelli P. et al.Update on dermoscopy of Spitz/Reed naevi and management guidelines by the International Dermoscopy Society.Br J Dermatol. 2017; 177: 645-655Crossref PubMed Scopus (50) Google Scholar). Histopathological characteristics pointing to melanoma include asymmetry, large cell size, ulceration, and frequent mitosis (Harms et al., 2015Harms K.L. Lowe L. Fullen D.R. Harms P.W. Atypical Spitz tumors: A diagnostic challenge.Arch Pathol Lab Med. 2015; 139: 1263-1270Crossref PubMed Scopus (40) Google Scholar). Since ASTs are defined by their borderline features, consensus in diagnostic criteria is difficult to establish, leaving this diagnostic, and consequently prognostic determination left to the individual pathologist (Gerami et al., 2014Gerami P. Busam K. Cochran A. Cook M.G. Duncan L.M. Elder D.E. et al.Histomorphologic assessment and interobserver diagnostic reproducibility of atypical spitzoid melanocytic neoplasms With long-term follow-up.Am J Surg Pathol. 2014; 38: 934-940Crossref PubMed Scopus (106) Google Scholar). One stratification using a scoring system places ASTs into high and low risk categories based on the patient’s age, size of lesion, presence of ulceration, and mitotic activity; increasing scores suggest higher chance of malignancy (Lyon, 2010Lyon V.B. The Spitz nevus: review and update.Clin Plast Surg. 2010; 37: 21-33Abstract Full Text Full Text PDF PubMed Scopus (24) Google Scholar). Recently, ancillary studies, such as immunohistochemical staining, comparative genomic hybridization, and fluorescence in situ hybridization (FISH), have proven to be potentially promising adjunctive tools to aid in diagnosis (Harms et al., 2015Harms K.L. Lowe L. Fullen D.R. Harms P.W. Atypical Spitz tumors: A diagnostic challenge.Arch Pathol Lab Med. 2015; 139: 1263-1270Crossref PubMed Scopus (40) Google Scholar).In terms of treatment, most specialists make a recommendation based on patient age, presence of cytological atypia, mitotic rate, lesion morphology, and possibly immunohistochemical and molecular studies (Harms et al., 2015Harms K.L. Lowe L. Fullen D.R. Harms P.W. Atypical Spitz tumors: A diagnostic challenge.Arch Pathol Lab Med. 2015; 139: 1263-1270Crossref PubMed Scopus (40) Google Scholar). CSN treatment is surgical with the aim to completely remove the lesion, although whether these benign tumors should be removed in children remains a topic of discussion (Harms et al., 2015Harms K.L. Lowe L. Fullen D.R. Harms P.W. Atypical Spitz tumors: A diagnostic challenge.Arch Pathol Lab Med. 2015; 139: 1263-1270Crossref PubMed Scopus (40) Google Scholar). Treatment for Spitzoid melanomas follows the National Comprehensive Cancer Network Guidelines for melanoma (Harms et al., 2015Harms K.L. Lowe L. Fullen D.R. Harms P.W. Atypical Spitz tumors: A diagnostic challenge.Arch Pathol Lab Med. 2015; 139: 1263-1270Crossref PubMed Scopus (40) Google Scholar). Treatment for ASTs varies among physicians, with some recommending full excision and continuous follow-up (Harms et al., 2015Harms K.L. Lowe L. Fullen D.R. Harms P.W. Atypical Spitz tumors: A diagnostic challenge.Arch Pathol Lab Med. 2015; 139: 1263-1270Crossref PubMed Scopus (40) Google Scholar).Discussion of incorrect answers:b.Melanoma: Melanoma results from malignant transformation of melanocytes, most usually in the skin. Males and females are at similar risk. The ABCDE pneumonic allows identification of melanoma to be simplified: asymmetric appearance, borders that appear blurry or irregular, color that changes in different areas, diameter larger than a pencil eraser, and evolving over time (Heistein, 2019Heistein J.B. Melanoma.https://emedicine.medscape.com/article/1295718-overviewDate: 2019Google Scholar, Rajabi-Estarabadi et al., 2017Rajabi-Estarabadi A. Tsatalis J. Williams N. AlGain M. Albreakan R. Moore K.J. et al.Cells to surgery quiz: November 2017.J Invest Dermatol. 2017; 137: e195Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar). Melanomas are classified by their growth pattern and can be organized into four major types. Superficial spreading melanomas represent most melanomas and appear as either single cells along the dermal-epidermal junction or in nests (Rajabi-Estarabadi et al., 2017Rajabi-Estarabadi A. Tsatalis J. Williams N. AlGain M. Albreakan R. Moore K.J. et al.Cells to surgery quiz: November 2017.J Invest Dermatol. 2017; 137: e195Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar). Cells may move to the stratum corneum or stratum granulosum or invade the papillary dermis. Nodular melanoma is characterized by vertical cell growth into the dermis. Lentigo maligna melanoma appears as spindle-shaped nests composed of irregularly shaped hyperchromatic cells. In acral lentiginous melanoma, cell proliferation occurs along the dermal-epidermal junction, as well as microinvasion into the papillary dermis. Dermatoscopic evaluation of melanoma includes a blue-white veil, scar-like depigmentation, and negative pigment network (Oakley, 2008Oakley A. Dermatoscopy.https://dermnetnz.org/cme/dermoscopy-course/Date: 2008Google Scholar, Rajabi-Estarabadi et al., 2017Rajabi-Estarabadi A. Tsatalis J. Williams N. AlGain M. Albreakan R. Moore K.J. et al.Cells to surgery quiz: November 2017.J Invest Dermatol. 2017; 137: e195Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar). Although ASTs can have many histological characteristics related to melanoma as seen in Spitzoid melanomas, ASTs are commonly elevated and may crust or ulcer on the surface (Kamino, 2009Kamino H. Spitzoid melanoma.Clin Dermatol. 2009; 27: 545-555Abstract Full Text Full Text PDF PubMed Scopus (39) Google Scholar).c.Melanocytic nevus: Melanocytic nevi are more common in individuals with pale skin and light-colored eyes. Acquired melanocytic nevi are generally less than 1 cm in diameter and evenly pigmented. Clinically these are typically flat, circumscribed, small macular lesions with variable pigmentation (Gerami and Busam, 2019Gerami P. Busam K.J. Acquired melanocytic nevi.in: Busam K.J. Gerami P. Scolyer R.A. Pathology of Melanocytic Tumors. Elsevier, Philadelphia2019: 8-25Crossref Google Scholar). Benign Spitz nevi, on the contrary, usually have no pigmentation and are dome-shaped lesions (Lyon, 2010Lyon V.B. The Spitz nevus: review and update.Clin Plast Surg. 2010; 37: 21-33Abstract Full Text Full Text PDF PubMed Scopus (24) Google Scholar). In dermoscopy, melanocytic nevi usually have a reticulated pattern, accumulation of the pigment along the rete ridges, and the clear spaces between the network that correspond to dermal papillae where there is usually less pigment (Gerami and Busam, 2019Gerami P. Busam K.J. Acquired melanocytic nevi.in: Busam K.J. Gerami P. Scolyer R.A. Pathology of Melanocytic Tumors. Elsevier, Philadelphia2019: 8-25Crossref Google Scholar). On histology, there is a proliferation of melanocytes as solitary units and small well-formed nests, preferentially at the tips of the rete ridges. In most lesions, there is a mix of solitary cells and nests of melanocytes at the dermoepidermal junction (Gerami and Busam, 2019Gerami P. Busam K.J. Acquired melanocytic nevi.in: Busam K.J. Gerami P. Scolyer R.A. Pathology of Melanocytic Tumors. Elsevier, Philadelphia2019: 8-25Crossref Google Scholar).d.Infantile hemangioma: Infantile hemangiomas, also known as strawberry hemangiomas, are benign tumors that commonly affect children. These proliferations are unique in their ability to involute and regress without treatment. Because superficial, localized capillary hemangiomas usually do not require medical intervention, the ability to consistently and accurately distinguish them from lesions of more malignant etiology is crucial (Satterfield and Chambers, 2019Satterfield K.R. Chambers C.B. Current treatment and management of infantile hemangiomas.Surv Ophthalmol. 2019; 64: 608-618Abstract Full Text Full Text PDF PubMed Scopus (31) Google Scholar). Clinically, the superficial subtypes of infantile hemangiomas are classically bright reddish in color and round with distinct borders. Deeper subtypes may manifest with a bluish hue (Satterfield and Chambers, 2019Satterfield K.R. Chambers C.B. Current treatment and management of infantile hemangiomas.Surv Ophthalmol. 2019; 64: 608-618Abstract Full Text Full Text PDF PubMed Scopus (31) Google Scholar). Lesions may be considered to be complicated if ulceration is present or if there is involvement of visceral organs, but there is no agreed upon criteria for complicated lesions. Infantile hemangiomas can be clinically diagnosed most of the time, but imaging may be used to aid diagnosis of challenging cases.e.Benign fibrous histiocytoma: Benign fibrous histiocytomas (BFHs) are benign solitary neoplasms composed of fibroblastic and histiocytic cell types (Ding and Hao, 2013Ding Y.F. Hao S.P. Benign fibrous histiocytoma of the cheek.Am J Otolaryngol. 2013; 34: 154-157Crossref PubMed Scopus (7) Google Scholar). Fibrous histiocytomas (FHs) typically occur on the skin of extremities as a solid, firm, and often hyperpigmented nodule but can sometimes occur in deep soft tissue, particularly in the head and neck region. The diagnosis of BFH is challenging and often relies on a combination of histopathology and immunohistochemistry (Ding and Hao, 2013Ding Y.F. Hao S.P. Benign fibrous histiocytoma of the cheek.Am J Otolaryngol. 2013; 34: 154-157Crossref PubMed Scopus (7) Google Scholar). Histopathologic findings include a proliferation of spindle and histiocyte-like cells as well as inflammatory cells (Luzar and Calonje, 2010Luzar B. Calonje E. Cutaneous fibrohistiocytic tumors - an update.Histopathology. 2010; 56: 148-165Crossref PubMed Scopus (82) Google Scholar). Whether BFH represents a neoplastic process or an inflammatory response has been debated. The etiology of BFH is often linked to inflammation typically caused by a bite or ruptured follicle with neutrophils and fibroblasts, among others, involved in the inflammatory response (Zelger et al., 2004Zelger B. Zelger B.G. Burgdorf W.H. Dermatofibroma-a critical evaluation.Int J Surg Pathol. 2004; 12: 333-344Crossref PubMed Scopus (56) Google Scholar). Many cases of histiocytoma are clinically mistakenly diagnosed for STs but can be differentiated based on histopathology. Presence of a biphasic cell population of histiocytes and fibroblasts are characteristic, and positivity for CD68 and vimentin confirms the cell population on immunohistochemistry (Ding and Hao, 2013Ding Y.F. Hao S.P. Benign fibrous histiocytoma of the cheek.Am J Otolaryngol. 2013; 34: 154-157Crossref PubMed Scopus (7) Google Scholar). It is also important to differentiate BFH from malignant FH, which is identified by pleomorphic sarcomatous cells, benign giant cells, and mitotic figures (Ding and Hao, 2013Ding Y.F. Hao S.P. Benign fibrous histiocytoma of the cheek.Am J Otolaryngol. 2013; 34: 154-157Crossref PubMed Scopus (7) Google Scholar). With many different variants of histiocytoma, characterization is crucial to properly diagnose and treat these lesions and differentiate benign from malignant variants to prevent reoccurrence and possible metastasis (Alves et al., 2014Alves J.V.P. Matos D.M. Barreiros H.F. Bártolo E.A. Variants of dermatofibroma--a histopathological study.An Bras Dermatol. 2014; 89: 472-477Crossref PubMed Scopus (61) Google Scholar).2.What is false about the management and/or prognosis of atypical Spitz tumors (ASTs)?CORRECT ANSWER: c. Sentinel lymph node biopsy improves the prognosis for patients with AST.The decision to perform a sentinel lymph node biopsy (SLNB) in patients with ASTs is a debated subject. In the past, SLNB was recommended for cases of ASTs as a diagnostic technique to approximate the malignant potential of the neoplasm. However, Lallas et al., 2014Lallas A. Kyrgidis A. Ferrara G. Kittler H. Apalla Z. Castagnetti F. et al.Atypical Spitz tumours and sentinel lymph node biopsy: a systematic review.Lancet Oncol. 2014; 15: e178-e183Abstract Full Text Full Text PDF PubMed Scopus (103) Google Scholar conducted a systematic review of 541 patients with ASTs and concluded that SLNB followed by lymphadenectomy did not improve prognosis. Regional nodal metastases are not associated with the development of more aggressive disease or worsened mortality; therefore, performing an SLNB for AST is not routinely recommended, especially for pediatric patients. Wide excision with clear margins and clinical follow-up is sufficient management.Discussion of incorrect answers:a.The diameter of the lesion should be considered in risk stratification of pediatric AST: Standard Spitz nevi are typically small and less than 6 mm in diameter, whereas ASTs are larger in diameter and occasionally greater than 10 mm. Spatz et al., 1999Spatz A. Calonje E. Handfield-Jones S. Barnhill R.L. Spitz tumors in children: a grading system for risk stratification.Arch Dermatol. 1999; 135: 282-285Crossref PubMed Google Scholar conducted a study of 30 patients with ASTs in children and adolescents to develop a scoring system based on the risk of metastases. Of the 30 patients, 11 had histological documentation of metastases. Those without metastases were followed for at least three years. The authors found that a lesion diameter greater than 10.0 mm carried a conditional probability of 1.72. Therefore, lesion diameter is an important feature to consider in risk stratification of pediatric ASTs. In addition, other features that exhibited probabilities greater than 1.5 included an age at diagnosis greater than 10 years, the presence of ulceration, involvement of subcutis, and a mitotic activity of at least 6 per mm2, all of which should also be included in risk stratification. More recent studies, such as that by Quan et al., 2020Quan V.L. Zhang B. Zhang Y. Mohan L.S. Shi K. Wagner A. et al.Integrating next-generation sequencing with morphology improves prognostic and biologic classification of Spitz neoplasms.J Invest Dermatol. 2020; 140: 1599-1608Abstract Full Text Full Text PDF Scopus (23) Google Scholar, employ molecular studies to improve diagnosis and determine risk.b.Patients with histopathologically diagnosed ASTs should undergo excision with clear margins regardless of age: The histopathological diagnosis of AST should warrant excision with clear margins regardless of age (Lallas et al., 2017aLallas A. Apalla Z. Ioannides D. Lazaridou E. Kyrgidis A. Broganelli P. et al.Update on dermoscopy of Spitz/Reed naevi and management guidelines by the International Dermoscopy Society.Br J Dermatol. 2017; 177: 645-655Crossref PubMed Scopus (50) Google Scholar). Given the ambiguity between the diagnosis of AST and Spitzoid melanoma, it is best to err on the side of caution and remove any Spitzoid tumor with atypical features. These may include infiltrative organization, poorly circumscribed borders, lack of Kamino bodies, subcutaneous involvement, and disrupted and ulcerated epidermis (Luo et al., 2011Luo S. Sepehr A. Tsao H. Spitz nevi and other Spitzoid lesions part I. Background and diagnoses.J Am Acad Dermatol. 2011; 65: 1073-1084Abstract Full Text Full Text PDF PubMed Scopus (67) Google Scholar). Proliferative and cytological features that suggest atypia, such as mitoses ≥2–6 per mm2, more heterogeneous cell types in addition to spindled or epithelioid cells, and a high nuclear to cytoplasmic ratio, are worrisome features. In contrast, presence of Kamino bodies, maturation, junctional clefting, and uniformity are good indicators of a benign Spitz nevus as opposed to AST (Crotty et al., 2002Crotty K.A. Scolyer R.A. Li L. Palmer A.A. Wang L. McCarthy S.W. Spitz naevus versus Spitzoid melanoma: when and how can they be distinguished?.Pathology. 2002; 34: 6-12Abstract Full Text PDF PubMed Scopus (99) Google Scholar). ASTs with positive margins should be re-excised with clear margins. Currently, there are not enough data to provide recommendations on the optimal margins; however, 3–5 mm margins are typically used (Massi et al., 2016Massi D. De Giorgi V. Mandala M. The complex management of atypical Spitz tumours.Pathology. 2016; 48: 132-141Abstract Full Text Full Text PDF PubMed Scopus (13) Google Scholar). After excision, it is important that the patient continues to follow-up with dermatology at least once annually for a skin exam and superficial node palpation.d.Patients with ASTs with sentinel lymph node involvement have better outcomes than patients with similar-staged conventional melanoma: Although patients with AST can develop sentinel lymph node involvement, their overall prognosis is better than patients with similar-staged standard melanoma. In a retrospective study of 57 ASTs that had SLNBs performed, 27 (47%) were positive and underwent complete dissection. At a median follow-up of 44 months, all patients were alive and free of disease (Ludgate et al., 2009Ludgate M.W. Fullen D.R. Lee J. Lowe L. Bradford C. Geiger J. et al.The atypical Spitz tumor of uncertain biologic potential: a series of 67 patients from a single institution.Cancer. 2009; 115: 631-641Crossref PubMed Scopus (159) Google Scholar). This is in contrast to conventional SLNB-positive melanomas (stage IIIA), which have a 5-year melanoma-specific survival of 93% (Morton et al., 2006Morton D.L. Thompson J.F. Cochran A.J. Mozzillo N. Elashoff R. Essner R. et al.Sentinel-node biopsy or nodal observation in melanoma.N Engl J Med. 2006; 355: 1307-1317Crossref PubMed Scopus (1460) Google Scholar). Therefore, ASTs with sentinel lymph node involvement seem to behave in a more indolent manner than conventional melanomas at this stage.e.The presence of TERT-p mutations is a predictor of recurrence: Differentiating ASTs from Spitzoid melanomas can be challenging both clinically and histologically. Therefore, additional molecular testing may be helpful to distinguish borderline lesions from malignant ones. In a study of 56 patients with either AST or Spitzoid melanoma, Lee et al., 2015Lee S. Barnhill R.L. Dummer R. Dalton J. Wu J. Pappo A. et al.TERT promoter mutations are predictive of aggressive clinical behavior in patients with Spitzoid melanocytic neoplasms.Sci Rep. 2015; 5: 11200Crossref PubMed Scopus (95) Google Scholar associated the presence of mutations in TERT-p via next-generation sequencing (NGS) with various histopathologic and prognostic parameters. They found that TERT-p mutations were present in all (n = 4) patients with hematogenous spread, but no mutations in this gene were found in those with favorable outcomes. Therefore, the presence of TERT-p mutations may predict recurrence. In addition, the presence of TERT-p mutations was also associated with ulceration and high mitotic levels and portended a poor prognosis. Ultimately, molecular testing for this mutation may be helpful in identifying high-risk subsets of ASTs.3.Quan et al., 2020Quan V.L. Zhang B. Zhang Y. Mohan L.S. Shi K. Wagner A. et al.Integrating next-generation sequencing with morphology improves prognostic and biologic classification of Spitz neoplasms.J Invest Dermatol. 2020; 140: 1599-1608Abstract Full Text Full Text PDF Scopus (23) Google Scholar performed DNA and RNA sequencing on 80 Spitz tumors (STs), 26 Spitz melanomas (SMs), and 22 melanomas with Spitzoid features (MSFs) to characterize the genomics of Spitz neoplasms and assess whether the integration of genomic data with morphological diagnosis improves classification and prognostication. All of the following are consistent with their findings, except:CORRECT ANSWER: c. Kinase fusions are detected in the MSF group.MSFs predominantly harbored known melanoma driver mutations, with ten BRAF (45%), six NRAS (27%), and two NF1 (9%) mutated cases. No kinase fusions were detected. The median tumor mutational burden was greater in MSF (9.7/Mb), and the median number of somatic mutations per case was 57. This was higher than the other groups with statistically significant P-values of 0.031 and 0.05, respectively. A total of 14 (64%) MSFs had TERT-p mutations and cooccurred with a BRAF or NRAS mutation in all instances.Discussion of incorrect answers:a.The ST group had a kinase fusion as the primary initiating genomic event in 73% of cases.b.Two new fusions, MYO5A-FGFR1 and MYO5A-ERBB4, are found in the ST group.Among the 80 STs, most (73%) harbored a kinase fusion in ALK, MAP3K8, BRAF, NTRK1, NTRK3, ROS1, RET, MET, RASGRF1, RAF1, and MAP3K3 or a truncating mutation in MAP3K8. mRNA expression analysis showed fusion transcripts to be highly expressed in all cases. Two previously not described fusions were identified: MYO5A-FGFR1 and MYO5A-ERBB4. In both cases, the 3′ kinase domain was preserved in the chimeric protein. A ROS1 mutation is also among the unreported initiating genomic events in STs described in this study.d.Classification incorporating genomic data was highly predictive of recurrence: Quan et al., 2020Quan V.L. Zhang B. Zhang Y. Mohan L.S. Shi K. Wagner A. et al.Integrating next-generation sequencing with morphology improves prognostic and biologic classification of Spitz neoplasms.J Invest Dermatol. 2020; 140: 1599-1608Abstract Full Text Full Text PDF Scopus (23) Google Scholar compared these three categories of Spitz neoplasms before and after a simple reclassification with NGS data, which simply moved all BRAF and NRAS cases from the ST or SM groups into the MSF group. Before reclassification, differences among the Kaplan–Meier curves for the ST, SM, and MSF groups were not statistically significant (P = 0.16). Conversely, after reclassification, moving all BRAF and NRAS mutated cases to the MSF group, the log-rank test (P = 0.0073) and pairwise comparison showed a significant difference of recurrence-free survival (RFS) between the ST and MSF groups (P = 0.017). RFS Kaplan–Meier curves were highly identical for the ST and SM groups. Specifically, six of the seven recurrences ended up in the MSF group. All cases with distant metastases and six of seven recurrences were either BRAF or NRAS mutated. Only a single ST with a MAP3K8 fusion from an 8-year-old child developed a local recurrence outside the scar after wide local excision.e.The classification and ability to predict the behavior of Spitz neoplasms can be improved by incorporating genomic data: Quan et al., 2020Quan V.L. Zhang B. Zhang Y. Mohan L.S. Shi K. Wagner A. et al.Integrating next-generation sequencing with morphology improves prognostic and biologic classification of Spitz neoplasms.J Invest Dermatol. 2020; 140: 1599-1608Abstract Full Text Full Text PDF Scopus (23) Google Scholar believe that the classification and ability to predict the behavior of Spitz neoplasms can be improved by incorporating genomic data. The vast majority of STs and SMs have chimeric fusions as the primary initiating genomic event and have a better prognosis than MSFs, which have frequent BRAF and NRAS mutations. When using genomics in the classification process, multiple parameters, including both principal component analysis and Kaplan–Meier analysis of RFS, suggest that SMs have more in common with STs than MSFs, that is, conventional melanomas with some Spitzoid cytomorphology." @default.
• W3044804760 created "2020-07-29" @default.
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• W3044804760 date "2020-08-01" @default.
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• W3044804760 title "Cells to Surgery Quiz: August 2020" @default.
• W3044804760 cites W1971159581 @default.
• W3044804760 cites W1971923037 @default.
• W3044804760 cites W1975359988 @default.
• W3044804760 cites W1988029602 @default.
• W3044804760 cites W1996910481 @default.
• W3044804760 cites W2105291861 @default.
• W3044804760 cites W2114611119 @default.
• W3044804760 cites W2119897469 @default.
• W3044804760 cites W2125478696 @default.
• W3044804760 cites W2133157220 @default.
• W3044804760 cites W2147722451 @default.
• W3044804760 cites W2155457860 @default.
• W3044804760 cites W2285042369 @default.
• W3044804760 cites W2332004731 @default.
• W3044804760 cites W2474154049 @default.
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