FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2989091275> ?p ?o ?g. }

• W2989091275 endingPage "e157" @default.
• W2989091275 startingPage "e151" @default.
• W2989091275 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 Chiang et al., 2019Chiang A. Tan C.Z. Kuonen F. Hodgkinson L.M. Chiang F. Cho R.J. et al.Genetic mutations underlying phenotypic plasticity in basosquamous carcinoma.J Invest Dermatol. 2019; 139: 2263-2271.e5Abstract Full Text Full Text PDF PubMed Scopus (14) Google Scholar (https://doi.org/10.1016/j.jid.2019.03.1163). Detailed answers and a list of relevant references are available following the Quiz Questions below. 1.What is your diagnosis?a.Pyoderma gangrenosumb.Basosquamous carcinomac.Keratoacanthomad.Basal cell carcinomae.Squamous cell carcinoma2.What is false about the management and/or prognosis of basosquamous carcinoma (BSC)?a.BSC with perineural involvement poses a greatly increased risk of recurrence.b.BSC has a metastatic capacity that is more similar to that of basal cell carcinoma (BCC) than squamous cell carcinoma (SCC).c.Mohs micrographic surgery provides the highest rate cure.d.Hedgehog inhibitors like vismodegib can be used in the treatment of metastatic BSC.e.If large nerves are involved, future work-up such as magnetic resonance imaging should be considered to evaluate the extent of the cancer.3.Chiang et al., 2019Chiang A. Tan C.Z. Kuonen F. Hodgkinson L.M. Chiang F. Cho R.J. et al.Genetic mutations underlying phenotypic plasticity in basosquamous carcinoma.J Invest Dermatol. 2019; 139: 2263-2271.e5Abstract Full Text Full Text PDF PubMed Scopus (14) Google Scholar conducted a mutational analysis of histologically confirmed BSCs compared with BCC and SCC samples to elucidate its genetic etiology and mechanisms for the observed phenotypic plasticity. All of the following are consistent with their findings, except:a.BSC contains genetic alterations in PTCH1 and SMO, similar to those of BCC.b.BSC lacks commonly found SCC driver mutations.c.ARID1A is highly mutated in BSC.d.Extracellular signal–regulated kinase (ERK) 1/2 activation is associated with squamatization in BSC.e.BSC contains genetic alterations in MYCN similar to those of SCC. See following pages for detailed answers. 1.What is your diagnosis?CORRECT ANSWER: b. Basosquamous carcinomaBasosquamous carcinoma (BSC) is a rare cutaneous neoplasm that displays both squamous cell and basal cell histology with a transition zone in between (de Faria, 1985de Faria J. Basal cell carcinoma of the skin with areas of squamous cell carcinoma: a basosquamous cell carcinoma?.J Clin Pathol. 1985; 38: 1273-1277Crossref PubMed Scopus (59) Google Scholar). BSC predominantly presents in fair-skinned older patients. It is commonly found in sun-exposed areas of the head and neck (82–97%), although tumors can also occur rarely on the trunk and extremities (Tan et al., 2017Tan C.Z. Rieger K.E. Sarin K.Y. Basosquamous carcinoma: controversy, advances, and future directions.Dermatol Surg. 2017; 43: 23-31Crossref PubMed Scopus (28) Google Scholar). BSC clinically presents as a nonspecific, rust-red, ulcerated lesion that can mimic several other pathologies (Giacomel et al., 2013Giacomel J. Lallas A. Argenziano G. Reggiani C. Piana S. Apalla Z. et al.Dermoscopy of basosquamous carcinoma.Br J Dermatol. 2013; 169: 358-364Crossref PubMed Scopus (37) Google Scholar). Dermoscopy may be useful in the initial diagnosis, typically appearing as a keratin mass with surface scaling, white structureless areas, and polymorphous vascular patterns (Akay et al., 2017Akay B.N. Saral S. Heper A.O. Erdem C. Rosendahl C. Basosquamous carcinoma: dermoscopic clues to diagnosis.J Dermatol. 2017; 44: 127-134Crossref PubMed Scopus (25) Google Scholar). The histology of biopsied samples is critical for the diagnosis of BSC, which is comprised of the following key characteristics: infiltrative growth of basaloid cells with scant cytoplasm and large, uniform, pale nuclei, in addition to aggregates of squamous cells containing abundant eosinophilic cytoplasm, found either near the center or scattered throughout the lesion (Leibovitch et al., 2005aLeibovitch I. Huilgol S.C. Selva D. Hill D. Richards S. Paver R. Cutaneous squamous cell carcinoma treated with Mohs micrographic surgery in Australia I. Experience over 10 years.J Am Acad Dermatol. 2005; 53: 253-260Abstract Full Text Full Text PDF PubMed Scopus (182) Google Scholar). Immunostaining for both Ber-EP4 and EMA is also useful to strengthen or confirm the diagnosis of BSC, as they are hallmarks of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), respectively (Volkenstein et al., 2010Volkenstein S. Wohlschlaeger J. Liebau J. Arens A. Lehnerdt G. Jahnke K. et al.Basosquamous carcinoma--a rare but aggressive skin malignancy.J Plast Reconstr Aesthet Surg. 2010; 63: e304-e306Abstract Full Text Full Text PDF PubMed Scopus (14) Google Scholar).Discussion of incorrect answers:a.Pyoderma gangrenosum: Pyoderma gangrenosum (PG) is an idiopathic rare skin disorder secondary to neutrophilic dermatosis. PG is common in young and middle-aged adults, with more women being affected (Binus et al., 2011Binus A.M. Qureshi A.A. Li V.W. Winterfield L.S. Pyoderma gangrenosum: a retrospective review of patient characteristics, comorbidities and therapy in 103 patients.Br J Dermatol. 2011; 165: 1244-1250Crossref PubMed Scopus (226) Google Scholar). Typical clinical findings of PG are painful ulcers with violaceous borders and purulent bases (Ruocco et al., 2009Ruocco E. Sangiuliano S. Gravina A.G. Miranda A. Nicoletti G. Pyoderma gangrenosum: an updated review.J Eur Acad Dermatol Venereol. 2009; 23: 1008-1017Crossref PubMed Scopus (332) Google Scholar). Its preferred locations include the lower extremities and trunk, though lesions may occur in other areas (Ruocco et al., 2009Ruocco E. Sangiuliano S. Gravina A.G. Miranda A. Nicoletti G. Pyoderma gangrenosum: an updated review.J Eur Acad Dermatol Venereol. 2009; 23: 1008-1017Crossref PubMed Scopus (332) Google Scholar). Atypical PG may present as a bullous, pustular, and/or vegetative form that is associated with different comorbidities (inflammatory bowel disease, inflammatory arthritis, and hematological cancer) (Callen, 1998Callen J.P. Pyoderma gangrenosum.Lancet. 1998; 351: 581-585Abstract Full Text Full Text PDF PubMed Scopus (359) Google Scholar). Clinical assessment must include a full history and physical exam to rule out other potential causes. The histological examination of the biopsy is critical to make a distinction between PG and BSC. There are no specific lab tests or staining markers to aid in the diagnosis of PG, as it is based on a ruling-out principle.c.Keratoacanthoma: Keratoacanthoma (KA) is a common skin tumor originating from hair follicles (Schwartz, 1994Schwartz R.A. Keratoacanthoma. J Am Acad Dermatol. 1994; 30: 1-19Abstract Full Text PDF PubMed Scopus (258) Google Scholar). It is likely underestimated because of misdiagnosis as SCC and its rapid resolution before presentation to physicians (Kwiek and Schwartz, 2016Kwiek B. Schwartz R.A. Keratoacanthoma (KA): an update and review.J Am Acad Dermatol. 2016; 74: 1220-1233Abstract Full Text Full Text PDF PubMed Scopus (104) Google Scholar). Light-skinned individuals in their late sixties are at the highest risk, with more men being affected. The most common subtype of KA is sporadic and solitary, whereas the familial or sporadic multiple-form is rare (Kwiek and Schwartz, 2016Kwiek B. Schwartz R.A. Keratoacanthoma (KA): an update and review.J Am Acad Dermatol. 2016; 74: 1220-1233Abstract Full Text Full Text PDF PubMed Scopus (104) Google Scholar). A typical solitary KA is found on sun-exposed areas (face, head, neck, and dorsum of extremities) but can also present on mucosal and genital areas (Savage et al., 2014Savage J.A. Maize J.C. Sr Keratoacanthoma clinical behavior: a systematic review.Am J Dermatopathol. 2014; 36: 422-429Crossref PubMed Scopus (56) Google Scholar). Its clinical presentation begins as a small, round, pink or skin-colored papule that rapidly progresses to a dome-shaped nodule with a central keratin plug. The dermoscopy of KA typically appears as a central crater with concentric circles and adjacent peripheral vessels (Cavicchini et al., 2013Cavicchini S. Tourlaki A. Lunardon L. Boneschi V. Gianotti R. Amelanotic melanoma mimicking keratoacanthoma: the diagnostic role of dermoscopy.Int J Dermatol. 2013; 52: 1023-1024Crossref PubMed Scopus (4) Google Scholar). However, this should not be used to make a distinction between KA and SCC. The histology of KA is also similar to SCC but can be differentiated by the following characteristics: more symmetry, more prominent epithelial lipping, a sharper demarcation between tumor and stroma, an enhanced ground-glass appearance, and less ulceration and pleomorphism (Kern and McCray, 1980Kern W.H. McCray M.K. The histopathologic differentiation of keratoacanthoma and squamous cell carcinoma of the skin.J Cutan Pathol. 1980; 7: 318-325Crossref PubMed Scopus (64) Google Scholar, Kwiek and Schwartz, 2016Kwiek B. Schwartz R.A. Keratoacanthoma (KA): an update and review.J Am Acad Dermatol. 2016; 74: 1220-1233Abstract Full Text Full Text PDF PubMed Scopus (104) Google Scholar). The immunohistochemistry may be helpful but does not yield a clear diagnostic value.d.Basal cell carcinoma: BCC is the most common skin cancer. The lifetime risk of developing BCC is as high as 20–30% (Bulliard et al., 2009Bulliard J.L. Panizzon R.G. Levi F. [Epidemiology of epithelial skin cancers].Rev Med Suisse. 2009; 5 (882, 884–8[in French])PubMed Google Scholar). Age and male sex are two independent risk factors for BCC (Lomas et al., 2012Lomas A. Leonardi-Bee J. Bath-Hextall F. A systematic review of worldwide incidence of nonmelanoma skin cancer.Br J Dermatol. 2012; 166: 1069-1080Crossref PubMed Scopus (1126) Google Scholar). BCC mainly affects sun-exposed areas, with 85% of cases occurring on the head and neck, whereas the trunk and limbs are less commonly affected (Kyrgidis et al., 2010Kyrgidis A. Vahtsevanos K. Tzellos T.G. Xirou P. Kitikidou K. Antoniades K. et al.Clinical, histological and demographic predictors for recurrence and second primary tumours of head and neck basal cell carcinoma. A 1062 patient-cohort study from a tertiary cancer referral hospital.Eur J Dermatol. 2010; 20: 276-282PubMed Google Scholar). There are four major types of BCC based upon distinctive pathologies: (i) nodular, (ii) superficial, (iii) morpheaform, and (iv) fibroepithelial (also known as fibroepithelioma of Pinkus) (Nakayama et al., 2011Nakayama M. Tabuchi K. Nakamura Y. Hara A. Basal cell carcinoma of the head and neck.J Skin Cancer. 2011; 2011: 496910Crossref PubMed Google Scholar). Dermoscopy is helpful in differentiating BCC from other skin lesions, with typical dermoscopic features including ulceration, multiple blue-gray globules, spoke wheel areas, leaf-like areas, and telangiectasias (Menzies et al., 2000Menzies S.W. Westerhoff K. Rabinovitz H. Kopf A.W. McCarthy W.H. Katz B. Surface microscopy of pigmented basal cell carcinoma.Arch Dermatol. 2000; 136: 1012-1016Crossref PubMed Scopus (288) Google Scholar). It can be challenging to differentiate BSC from other types of BCCs, as they are commonly seen on the face and neck and share a certain level of histology. Carefully examining the biopsy is critical in properly diagnosing BSC. On histology, typical BCC displays small hyperchromatic cells with peripheral palisading nuclei and stromal collagen deposition with proliferative fibroblasts. In contrast, BSC exhibits eosinophilic cytoplasm, often lacks the characteristic peripheral palisading and retraction artifact, and has variable cytoplasmic keratinization (Garcia et al., 2009Garcia C. Poletti E. Crowson A.N. Basosquamous carcinoma.J Am Acad Dermatol. 2009; 60: 137-143Abstract Full Text Full Text PDF PubMed Scopus (115) Google Scholar). Immunostaining for both Ber-EP4 and EMA is also helpful to eliminate the diagnosis of pure BCC, as it does not express EMA.e.Squamous cell carcinoma: SCC is the second most common skin malignancy and demonstrates more aggressive features than BCC (Ting et al., 2005Ting P.T. Kasper R. Arlette J.P. Metastatic basal cell carcinoma: report of two cases and literature review.J Cutan Med Surg. 2005; 9: 10-15Crossref PubMed Scopus (127) Google Scholar). It is commonly found among the elderly population, with males and individuals with fair skin types at higher risk (Xiang et al., 2014Xiang F. Lucas R. Hales S. Neale R. Incidence of nonmelanoma skin cancer in relation to ambient UV radiation in white populations, 1978–2012: empirical relationships.JAMA Dermatol. 2014; 150: 1063-1071Crossref PubMed Scopus (157) Google Scholar). In addition to UV exposure, immunosuppressive conditions or medications are risk factors for the development of SCC (Fortina et al., 2004Fortina A.B. Piaserico S. Caforio A.L. Abeni D. Alaibac M. Angelini A. et al.Immunosuppressive level and other risk factors for basal cell carcinoma and squamous cell carcinoma in heart transplant recipients.Arch Dermatol. 2004; 140: 1079-1085Crossref PubMed Scopus (101) Google Scholar; Ramsay et al., 2007Ramsay H.M. Reece S.M. Fryer A.A. Smith A.G. Harden P.N. Seven-year prospective study of nonmelanoma skin cancer incidence in U.K. renal transplant recipients.Transplantation. 2007; 84: 437-439Crossref PubMed Scopus (57) Google Scholar). Certain anatomic sites are considered high-risk for metastasis, including the face, ears, pre- and post-auricular areas, genitalia, hands, and feet (Burton et al., 2016Burton K.A. Ashack K.A. Khachemoune A. Cutaneous squamous cell carcinoma: a review of high-risk and metastatic disease.Am J Clin Dermatol. 2016; 17: 491-508Crossref PubMed Scopus (164) Google Scholar). The typical clinical presentation of in situ SCC is a skin-colored to erythematous well-demarcated scaly patch or plaque. There are other variants of SCC in the genital and mucosal areas that present with distinct phenotypes. Dermoscopy typically shows keratin and white circles, which aids in differentiating SCCs from actinic keratosis and Bowen disease, but is not helpful in differentiating SCC from BSC (Rosendahl et al., 2012Rosendahl C. Cameron A. Argenziano G. Zalaudek I. Tschandl P. Kittler H. Dermoscopy of squamous cell carcinoma and keratoacanthoma.Arch Dermatol. 2012; 148: 1386-1392Crossref PubMed Scopus (123) Google Scholar). Histological examination and/or immunohistochemistry are essential in confirming whether the lesion is pure SCC or BSC.2.What is false about the management and/or prognosis of basosquamous carcinoma (BSC)?CORRECT ANSWER: b. BSC has a metastatic capacity that is more similar to that of basal cell carcinoma (BCC) than squamous cell carcinoma (SCC).Although BSC is technically a subtype of BCC, this tumor behaves more like SCC. BSC shares histologic features of both BCC and SCC; however, BSC is more aggressive than BCC. It carries a higher risk of metastasizing than BCC and possibly even SCC (Costantino et al., 2006Costantino D. Lowe L. Brown D.L. Basosquamous carcinoma-an under-recognized, high-risk cutaneous neoplasm: case study and review of the literature.J Plast Reconstr Aesthet Surg. 2006; 59: 424-428Abstract Full Text Full Text PDF PubMed Scopus (50) Google Scholar). The incidence of metastasis for BSC is estimated to be greater than 5% (O’Toole et al., 2012O’Toole E.A. Pontén F. Lundeberg J. Asplund A. Principles of tumor biology and pathogenesis of BCCs and SCCs.in: Bolognia J.L. Dermatology. 3rd ed. Elsevier, London, United Kingdom2012: 1872-1893Google Scholar). In comparison, the incidence of regional nodal metastases for SCC is 3.7–5.2% and less than 0.1% for BCC (Brantsch et al., 2008Brantsch K.D. Meisner C. Schönfisch B. Trilling B. Wehner-Caroli J. Röcken M. et al.Analysis of risk factors determining prognosis of cutaneous squamous-cell carcinoma: a prospective study.Lancet Oncol. 2008; 9: 713-720Abstract Full Text Full Text PDF PubMed Scopus (695) Google Scholar; Brougham et al., 2012Brougham N.D. Dennett E.R. Cameron R. Tan S.T. The incidence of metastasis from cutaneous squamous cell carcinoma and the impact of its risk factors.J Surg Oncol. 2012; 106: 811-815Crossref PubMed Scopus (200) Google Scholar, Karia et al., 2014Karia P.S. Jambusaria-Pahlajani A. Harrington D.P. Murphy G.F. Qureshi A.A. Schmults C.D. Evaluation of American Joint Committee on Cancer, International Union Against Cancer, and Brigham and Women's Hospital tumor staging for cutaneous squamous cell carcinoma.J Clin Oncol. 2014; 32: 327-334Crossref PubMed Scopus (201) Google Scholar, Mourouzis et al., 2009Mourouzis C. Boynton A. Grant J. Umar T. Wilson A. Macpheson D. et al.Cutaneous head and neck SCCs and risk of nodal metastasis - UK experience.J Craniomaxillofac Surg. 2009; 37: 443-447Crossref PubMed Scopus (118) Google Scholar, Paver et al., 1973Paver K. Poyzer K. Burry N. Deakin M. The incidence of basal cell carcinoma and their metastases in Australia and New Zealand[letter].Australas J Dermatol. 1973; 14: 53Crossref PubMed Google Scholar, Schmults et al., 2013Schmults C.D. Karia P.S. Carter J.B. Han J. Qureshi A.A. Factors predictive of recurrence and death from cutaneous squamous cell carcinoma: a 10-year, single-institution cohort study.JAMA Dermatol. 2013; 149: 541-547Crossref PubMed Scopus (329) Google Scholar, von Domarus and Stevens, 1984von Domarus H. Stevens P.J. Metastatic basal cell carcinoma. Report of five cases and review of 170 cases in the literature.J Am Acad Dermatol. 1984; 10: 1043-1060Abstract Full Text PDF PubMed Scopus (373) Google Scholar). In studying the incidence of metastases for BSC, Martin et al., 2000Martin 2nd, R.C. Edwards M.J. Cawte T.G. Sewell C.L. McMasters K.M. Basosquamous carcinoma: analysis of prognostic factors influencing recurrence.Cancer. 2000; 88: 1365-1369Crossref PubMed Scopus (128) Google Scholar found that, of 28 patients with BSC, five patients developed lymph node metastases, one of which also had pulmonary metastasis. Another study evaluated 1,000 consecutive Mohs cases and found that two of 228 cases of patients with SCC had pulmonary metastases (0.87%), compared with two of 27 patients with BSC (7.4%) (Bowman et al., 2003Bowman P.H. Ratz J.L. Knoepp T.G. Barnes C.J. Finley E.M. Basosquamous carcinoma.Dermatol Surg. 2003; 29 ([discussion 833]): 830-832Crossref PubMed Scopus (92) Google Scholar). Similarly, a more recent study revealed that 11 of 142 (7.7%) patients with BSC had sentinel lymph node micrometastasis (Kakagia et al., 2018Kakagia D.D. Zapandioti P. Trypsiannis G. Grekou A.N. Tsoutsos D. Sentinel lymph node metastasis in primary cutaneous basosquamous carcinoma. A cross-sectional study.J Surg Oncol. 2018; 117: 1752-1758Crossref PubMed Scopus (4) Google Scholar). Furthermore, whether BSC arises de novo or originates from a pre-existing BCC continues to be under debate. For instance, a study that reanalyzed cases of metastatic BCC discovered that 80% of the lesions initially diagnosed as BCC had basosquamous histology of the metastasis (Farmer and Helwig, 1980Farmer E.R. Helwig E.B. Metastatic basal cell carcinoma: a clinicopathologic study of seventeen cases.Cancer. 1980; 46: 748-757Crossref PubMed Scopus (221) Google Scholar).Discussion of incorrect answers:a.BSC with perineural involvement poses a greatly increased risk of recurrence. Perineural growth, also referred to as perineural invasion, is a classic indicator of aggressive disease for any cutaneous malignancy (Buchanan et al., 2014Buchanan L. De'Ambrosis B. DeAmbrosis K. Warren T. Huilgol S. Soyer H.P. et al.Defining incidental perineural invasion: the need for a national registry.Australas J Dermatol. 2014; 55: 107-110Crossref PubMed Scopus (14) Google Scholar). Along with a tumor size >2 cm and lymphatic invasion, perineural involvement is a significant determinant for sentinel lymph node micrometastasis (Kakagia et al., 2018Kakagia D.D. Zapandioti P. Trypsiannis G. Grekou A.N. Tsoutsos D. Sentinel lymph node metastasis in primary cutaneous basosquamous carcinoma. A cross-sectional study.J Surg Oncol. 2018; 117: 1752-1758Crossref PubMed Scopus (4) Google Scholar). In addition, a case report by Amram et al., 2018Amram A.L. Hertzing W.J. Smith S.V. Chévez-Barrios P. Lee A.G. Perineural spread of basosquamous carcinoma to the orbit, cavernous sinus, and infratemporal fossa.Orbit. 2018; 37: 110-114Crossref PubMed Scopus (3) Google Scholar described a patient with BSC causing perineural invasion that led to metastases of the orbit, cavernous sinus, and infratemporal fossa. Furthermore, Martin et al., 2000Martin 2nd, R.C. Edwards M.J. Cawte T.G. Sewell C.L. McMasters K.M. Basosquamous carcinoma: analysis of prognostic factors influencing recurrence.Cancer. 2000; 88: 1365-1369Crossref PubMed Scopus (128) Google Scholar discovered that male sex, positive surgical resection margins, lymphatic invasion, and perineural involvement were all significant predictors of BSC recurrence.c.Mohs micrographic surgery provides the highest rate cure. The standard therapy for BSC is Mohs micrographic surgery (Allen et al., 2014Allen K.J. Cappel M.A. Killian J.M. Brewer J.D. Basosquamous carcinoma and metatypical basal cell carcinoma: a review of treatment with Mohs micrographic surgery.Int J Dermatol. 2014; 53: 1395-1403Crossref PubMed Scopus (19) Google Scholar, Leibovitch et al., 2005bLeibovitch I. Huilgol S.C. Selva D. Richards S. Paver R. Basosquamous carcinoma: treatment with Mohs micrographic surgery.Cancer. 2005; 104: 170-175Crossref PubMed Scopus (64) Google Scholar, Skaria, 2010Skaria A.M. Recurrence of basosquamous carcinoma after Mohs micrographic surgery.Dermatology. 2010; 221: 352-355Crossref PubMed Scopus (21) Google Scholar). Mohs micrographic surgery reduces the recurrence rate of BSC to about 4–9% (Wermker et al., 2015Wermker K. Roknic N. Goessling K. Klein M. Schulze H.J. Hallermann C. Basosquamous carcinoma of the head and neck: clinical and histologic characteristics and their impact on disease progression.Neoplasia. 2015; 17: 301-305Crossref PubMed Scopus (24) Google Scholar). This is in comparison to recurrence frequencies between 12% and 51% demonstrated in older studies that did not employ the use of histographic-controlled Mohs surgery (Borel, 1973Borel D.M. Cutaneous basosquamous carcinoma. Review of the literature and report of 35 cases.Arch Pathol. 1973; 95: 293-297PubMed Google Scholar; Schuller et al., 1979Schuller D.E. Berg J.W. Sherman G. Krause C.J. Cutaneous basosquamous carcinoma of the head and neck: a comparative analysis.Otolaryngol Head Neck Surg (1979). 1979; 87: 420-427Crossref PubMed Scopus (64) Google Scholar). Of note, the recurrence rate of BSC is still significantly higher than that of BCC (0.64%) and SCC (1.2%) after Mohs surgery (Alam et al., 2015Alam M. Desai S. Nodzenski M. Dubina M. Kim N. Martini M. et al.Active ascertainment of recurrence rate after treatment of primary basal cell carcinoma (BCC).J Am Acad Dermatol. 2015; 73: 323-325Abstract Full Text Full Text PDF PubMed Scopus (6) Google Scholar; Belkin and Carucci, 2011Belkin D. Carucci J.A. Mohs surgery for squamous cell carcinoma.Dermatol Clin. 2011; 29 (vii, vii): 161-174Abstract Full Text Full Text PDF PubMed Scopus (24) Google Scholar).d.Hedgehog inhibitors like vismodegib can be used in the treatment of metastatic BSC. The use of Hedgehog (Hh) pathway inhibitors is a relatively recent therapeutic option for patients with advanced or metastatic BCC. Activating mutations in SMO or inactivating mutations in PTCH leads to activation of the Hedgehog-patched signaling pathway, which has been associated with the development of BCC (O’Toole et al., 2012O’Toole E.A. Pontén F. Lundeberg J. Asplund A. Principles of tumor biology and pathogenesis of BCCs and SCCs.in: Bolognia J.L. Dermatology. 3rd ed. Elsevier, London, United Kingdom2012: 1872-1893Google Scholar). Vismodegib, an Hh pathway inhibitor, binds to the protein SMO, which was found to have antitumor activity in metastatic BCC (Von Hoff et al., 2009Von Hoff D.D. LoRusso P.M. Rudin C.M. Reddy J.C. Yauch R.L. Tibes R. et al.Inhibition of the hedgehog pathway in advanced basal-cell carcinoma.N Engl J Med. 2009; 361: 1164-1172Crossref PubMed Scopus (919) Google Scholar). Other drugs with this mechanism of action include sonidegib and itraconazole. A recent case report demonstrated complete regression of a locally giant advanced BSC with bone involvement after only 7 months of treatment with vismodegib (Sahuquillo-Torralba et al., 2019Sahuquillo-Torralba A. Llavador-Ros M. Caballero-Daroqui J. Botella-Estrada R. Complete response of a locally advanced basosquamous carcinoma with vismodegib treatment.Indian J Dermatol Venereol Leprol. 2019; 85: 549-552Crossref PubMed Scopus (4) Google Scholar). In addition, a case series determined that two patients with BSC with proven mutations in the Hh pathway had clinical response to vismodegib and sonidegib, whereas another patient without the mutation did not. Therefore, Hh inhibitors are potential therapeutic options for patients with metastatic BSC, especially those with identified mutations in this pathway.e.If large nerves are involved, future work-up such as magnetic resonance imaging should be considered to evaluate the extent of the cancer. In patients with large or extensive perineural involvement of SCC, BCC, or BSC, imaging studies like magnetic resonance imaging (MRI) are recommended to evaluate the full extent of the cancer. Early detection and treatment have the potential to improve survival; however, the value of radiologic surveillance is not well established, especially for BSC. For SCC in particular, a recent study assessed a cohort of patients with perineural involvement and found that patients who underwent imaging were less likely to develop metastasis or other disease-related outcomes (Ruiz et al., 2017Ruiz E.S. Karia P.S. Morgan F.C. Schmults C.D. The positive impact of radiologic imaging on high-stage cutaneous squamous cell carcinoma management.J Am Acad Dermatol. 2017; 76: 217-225Abstract Full Text Full Text PDF PubMed Scopus (38) Google Scholar). Similarly, in a study of 12 patients with SCC and clinical and/or radiological evidence of perineural invasion, MRI revealed the full extent of disease and was useful in planning treatment in six cases (Gluck et al., 2009Gluck I. Ibrahim M. Popovtzer A. Teknos T.N. Chepeha D.B. Prince M.E. et al.Skin cancer of the head and neck with perineural invasion: defining the clinical target volumes based on the pattern of failure.Int J Radiat Oncol Biol Phys. 2009; 74: 38-46Abstract Full Text Full Text PDF PubMed Scopus (42) Google Scholar). Therefore, further imaging work-up should also be considered in patients with BSC and perineural involvement.3.Chiang et al., 2019Chiang A. Tan C.Z. Kuonen F. Hodgkinson L.M. Chiang F. Cho R.J. et al.Genetic mutations underlying phenotypic plasticity in basosquamous carcinoma.J Invest Dermatol. 2019; 139: 2263-2271.e5Abstract Full Text Full Text PDF PubMed Scopus (14) Google Scholar conducted a mutational analysis of histologically confirmed BSCs compared with BCC and SCC samples to elucidate its genetic etiology and mechanisms for the observed phenotypic plasticity. All of the following are consistent with their findings, except:CORRECT ANSWER: e. BSC contains genetic alterations in MYCN similar to those of SCC.Chiang et al., 2019Chiang A. Tan C.Z. Kuonen F. Hodgkinson L.M. Chiang F. Cho R.J. et al.Genetic mutations underlying phenotypic plasticity in basosquamous carcinoma.J Invest Dermatol. 2019; 139: 2263-2271.e5Abstract Full Text Full Text PDF PubMed Scopus (14) Google Scholar compared gene mutations among BSC and BCC. Mutations in MYCN, a recently described BCC cancer driver, were observed in 15% of the BSCs, compared with 19% of the BCC and 6% of the SCC samples. The presence of MYCN in the BSC samples provides genetic evidence that BSCs share cancer drivers similar to those of BCC and arise through the activation of Hh signaling.Discussion of incorrect answers:a.BSC contains genetic alterations in PTCH1 and SMO, similar to those of BCC. When comparing the genetic mutations among various skin cancers, Chiang et al.(2019) found that 45% of BSC tumors contained deleterious mutations in PTCH1, compared with 44% of the BCCs and 10% of the SCCs. The oncogenic SMO M2 mutation, W535L, was observed in 5% of the BSCs, compared with 25% of the BCCs and none (0%) of the SCC samples. The presence of PTCH, MYCN, and SMO in the BSC samples provides genetic evidence that BSCs share similar cancer drivers to those of BCC and arise through the activation of Hh signaling.b.BSC lacks commonly found SCC driver mutations. The researchers also compared genetic mutations between BSC and SCC. NOTCH1 and NOTCH2 mutations were observed in 15% and 20% of the BSC tumors, respectively, lower than the 46% and 37% of the SCC samples and more comparable to the frequencies observed in the BCCs (31% and 25%, respectively), suggesting that the BSCs do not harbor elevated NOTCH mutations at the frequency reported in SCCs. In addition, BSC also lacked oncogenic HRAS and KRAS mutations, which have been reported to be mutated in SCC. Finally, there were no CDKN2A mutations present in BSC compared with 15% of SCC samples. The differences in mutation frequencies suggest that BSC has a mutational landscape differing from SCC and lacks classic SCC driver mutations.c.ARID1A is highly mutated in BSC. The investigators also identified the top 20 cancer genes mutated in BSC. ARID1A was highly mutated in 45% of the BSCs compared with 19% of the BCC and 19% of the SCC tumors.d.Extracellular signal–regulated kinase (ERK) 1/2 activation is associated with squamatization in BSC. Chiang et al., 2019Chiang A. Tan C.Z. Kuonen F. Hodgkinson L.M. Chiang F. Cho R.J. et al.Genetic mutations underlying phenotypic plasticity in basosquamous carcinoma.J Invest Dermatol. 2019; 139: 2263-2271.e5Abstract Full Text Full Text PDF PubMed Scopus (14) Google Scholar also detected higher expression of phosphorylated ERK in the basaloid cells adjacent to the squamatized areas, indicating that activation of the RAS–mitogen-activated protein kinase (MAPK) pathway may drive squamatization with the subsequent loss of Gli1 expression as a secondary event. These results implicate the MAPK pathway in modulating the tumor plasticity observed in BSC." @default.
• W2989091275 created "2019-11-22" @default.
• W2989091275 creator A5005401964 @default.
• W2989091275 creator A5007101679 @default.
• W2989091275 creator A5067254519 @default.
• W2989091275 creator A5075007241 @default.
• W2989091275 creator A5080510239 @default.
• W2989091275 creator A5086806978 @default.
• W2989091275 date "2019-12-01" @default.
• W2989091275 modified "2023-09-27" @default.
• W2989091275 title "Cells to Surgery Quiz: December 2019" @default.
• W2989091275 cites W1529230314 @default.
• W2989091275 cites W1548627694 @default.
• W2989091275 cites W1594237846 @default.
• W2989091275 cites W1945299602 @default.
• W2989091275 cites W1965431780 @default.
• W2989091275 cites W1967585292 @default.
• W2989091275 cites W1969321968 @default.
• W2989091275 cites W1974131161 @default.
• W2989091275 cites W1978394325 @default.
• W2989091275 cites W1980886152 @default.
• W2989091275 cites W1984983462 @default.
• W2989091275 cites W1992077682 @default.
• W2989091275 cites W1994292344 @default.
• W2989091275 cites W1996800159 @default.
• W2989091275 cites W2003589889 @default.
• W2989091275 cites W2004151295 @default.
• W2989091275 cites W2011342967 @default.
• W2989091275 cites W2012302921 @default.
• W2989091275 cites W2023031488 @default.
• W2989091275 cites W2031908604 @default.
• W2989091275 cites W2055818502 @default.
• W2989091275 cites W2059179724 @default.
• W2989091275 cites W2068633911 @default.
• W2989091275 cites W2068910937 @default.
• W2989091275 cites W2070951010 @default.
• W2989091275 cites W2074857109 @default.
• W2989091275 cites W2081484831 @default.
• W2989091275 cites W2105410994 @default.
• W2989091275 cites W2108984907 @default.
• W2989091275 cites W2109272551 @default.
• W2989091275 cites W2115230424 @default.
• W2989091275 cites W2125914195 @default.
• W2989091275 cites W2157797076 @default.
• W2989091275 cites W2170144295 @default.
• W2989091275 cites W2171362247 @default.
• W2989091275 cites W2261513376 @default.
• W2989091275 cites W2318741789 @default.
• W2989091275 cites W2402806107 @default.
• W2989091275 cites W2404804781 @default.
• W2989091275 cites W2417195961 @default.
• W2989091275 cites W2461530997 @default.
• W2989091275 cites W2466943428 @default.
• W2989091275 cites W2513964115 @default.
• W2989091275 cites W2528186064 @default.
• W2989091275 cites W2765983877 @default.
• W2989091275 cites W2800620768 @default.
• W2989091275 cites W2951426938 @default.
• W2989091275 cites W2965634677 @default.
• W2989091275 cites W1655269061 @default.
• W2989091275 cites W2472582320 @default.
• W2989091275 doi "https://doi.org/10.1016/j.jid.2019.10.005" @default.
• W2989091275 hasPublicationYear "2019" @default.
• W2989091275 type Work @default.
• W2989091275 sameAs 2989091275 @default.
• W2989091275 citedByCount "0" @default.
• W2989091275 crossrefType "journal-article" @default.
• W2989091275 hasAuthorship W2989091275A5005401964 @default.
• W2989091275 hasAuthorship W2989091275A5007101679 @default.
• W2989091275 hasAuthorship W2989091275A5067254519 @default.
• W2989091275 hasAuthorship W2989091275A5075007241 @default.
• W2989091275 hasAuthorship W2989091275A5080510239 @default.
• W2989091275 hasAuthorship W2989091275A5086806978 @default.
• W2989091275 hasBestOaLocation W29890912751 @default.
• W2989091275 hasConcept C61434518 @default.
• W2989091275 hasConcept C71924100 @default.
• W2989091275 hasConceptScore W2989091275C61434518 @default.
• W2989091275 hasConceptScore W2989091275C71924100 @default.
• W2989091275 hasIssue "12" @default.
• W2989091275 hasLocation W29890912751 @default.
• W2989091275 hasOpenAccess W2989091275 @default.
• W2989091275 hasPrimaryLocation W29890912751 @default.
• W2989091275 hasRelatedWork W2019250753 @default.
• W2989091275 hasRelatedWork W2071494235 @default.
• W2989091275 hasRelatedWork W2102644969 @default.
• W2989091275 hasRelatedWork W2766770000 @default.
• W2989091275 hasRelatedWork W2770144974 @default.
• W2989091275 hasRelatedWork W2967287585 @default.
• W2989091275 hasRelatedWork W3208701539 @default.
• W2989091275 hasRelatedWork W4253573160 @default.
• W2989091275 hasRelatedWork W4313346385 @default.
• W2989091275 hasRelatedWork W4317816533 @default.
• W2989091275 hasVolume "139" @default.
• W2989091275 isParatext "false" @default.
• W2989091275 isRetracted "false" @default.
• W2989091275 magId "2989091275" @default.
• W2989091275 workType "article" @default.