Case Report Case Report AA WolfWolf in in Sheep’s Sheep’s Clothing: Clothing: Collision Collision of of Melanoma Melanoma and andKeratoacanthoma Keratoacanthoma
1, 1 2 MatthiasMatthias Walther Walther *,1,*, Sandra Sandra Falkvoll Falkvolland 1 and Sebastian Sebastian Leibl Leibl 2
1 1 Skinmed—ClinicSkinmed—Clinic forfor Dermatology,Dermatology, 5000 5000 Aarau, Aarau, Switzerland; Switzerland; [email protected] [email protected] 2 2 Skinpath—Histopathology,Skinpath—Histopathology, 5600 5600 Lenzburg, Lenzburg Switzerland;, Switzerland; [email protected] [email protected] ** Correspondence:Correspondence: [email protected]@skinmed.ch
Abstract:Abstract:Collision Collision tumorstumors consistingconsisting ofof melanomamelanoma andand squamoussquamous cellcell carcinomacarcinoma areare veryvery rare.rare. WeWe presentpresent the the casecase ofof aa deceptivedeceptive hyperkeratotichyperkeratotic nodule nodule on onthe theforearm forearm of ofa a 72-year-old72-year-old woman, woman, which which clinicallyclinically appeared appeared to to be be a squamousa squamous cell cell carcinoma, carcinoma, keratoacanthoma keratoacanthoma type. type Histological. Histological examination examina- surprisinglytion surprisingly revealed revealed a coexisting a coexisting epithelioid epithelioid melanoma. melanoma. Thus, this Thus, case this report case shows report the shows importance the im- ofportance an early of histopathological an early histopathological and immunohistochemical and immunohistochemical workup to preventworkup unnecessaryto prevent unnecessary diagnostic anddiagnostic therapeutic and therapeutic delay with negativedelay with effects negative on prognosis. effects on prognosis.
Keywords:Keywords:melanoma; melanoma; squamous squamous cell cell carcinoma; carcinoma; collision collision tumor; tumor; oncology; oncology; dermatopathology dermatopathology
1.1. CaseCase PresentationPresentation AA 72-year-old female female patient patient (Fitzpatrick (Fitzpatrick skin skin phototype phototype 2, no 2, nofamily family history history of mel- of melanoma)anoma) presented presented with with a slightly a slightly red, red, hyperker hyperkeratotic,atotic, and andcrusty crusty nodule nodule on her on right her right fore- forearmarm (Figure (Figure 1), which1), which had hadquickly quickly developed developed during during the last the few last months few months in sun-damaged in sun- Citation: Walther, M.; Falkvoll, S.; damagedskin with skinmultiple with solar multiple lentigines. solar Clinically, lentigines. the Clinically, lesion was the suspicious lesion was for suspicious squamous forcell Leibl,Citation: S. A WolfWalther, in Sheep’s M.; Falkvoll, Clothing: S.; squamouscarcinoma/keratoacanthoma. cell carcinoma/keratoacanthoma. The medical history The medical of the patient history was of theunremarkable patient was except unre- CollisionLeibl, S. ofA MelanomaWolf in Sheep’s and Clothing: markablefor arterial except hypertension for arterial and hypertension some actinic and keratoses some actinic in the keratosespast. in the past. Keratoacanthoma.Collision of MelanomaDermatopathology and 2021Keratoacanthoma., 8, 253–257. https://doi.org/ Dermatopathology 10.3390/dermatopathology80300302021, 8, x. https://doi.org/10.3390/xxxxx
AcademicAcademic Editor: Editor: Gürkan Gürkan Kaya Kaya
Received:Received: 30 30 May May 2021 2021 Accepted:Accepted: 2 2 July July 2021 2021 Published:Published: 4 date July 2021
Publisher’sPublisher’s Note: Note:MDPI MDPI stays stays neutral neu- withtral regardwith toregard jurisdictional to jurisdictional claims in publishedclaims in mapspublished and institutional maps and insti- affil- iations.tutional affiliations.
Copyright: © 2021 by the authors. Copyright: © 2021 by the authors. Submitted for possible open access Figure 1. Macroscopy, hyperkeratotic nodule on forearm. Licensee MDPI, Basel, Switzerland. Figure 1. Macroscopy, hyperkeratotic nodule on forearm. publication under the terms and This article is an open access article conditions of the Creative Com- ThreeThree weeksweeks afterafter thethe firstfirst consultation,consultation, the the nodulenodule was was excisedexcised with with aa safetysafety marginmargin distributed under the terms and mons Attribution (CC BY) license of about 3 mm. Surprisingly, histology revealed a collision tumor consisting of kera- conditions of the Creative Commons of about 3 mm. Surprisingly, histology revealed a collision tumor consisting of keratoa- (http://creativecommons.org/li- toacanthoma and melanoma with a Breslow thickness of 4.6 mm (Figure 2). Consequently, Attribution (CC BY) license (https:// canthoma and melanoma with a Breslow thickness of 4.6 mm (Figure2). Consequently, censes/by/4.0/). creativecommons.org/licenses/by/ thethe patientpatient was referred referred to to a a hospital hospital specialized specialized in inmelanoma melanoma for for further further diagnostics diagnostics and 4.0/). andtherapy therapy (PET-CT (PET-CT scan scan and and evaluation evaluation of sent of sentinelinel lymph lymph node node biopsy). biopsy). Unfortunately, Unfortunately, the
Dermatopathology 2021, 8, Firstpage–Lastpage. https://doi.org/10.3390/xxxxx www.mdpi.com/journal/dermatopathology Dermatopathology 2021, 8, 253–257. https://doi.org/10.3390/dermatopathology8030030 https://www.mdpi.com/journal/dermatopathology Dermatopathology 2021, 8 254 Dermatopathology 2021, 8, 2
the PET-CT scan showed pulmonary metastases, which were histologically confirmed byPET-CT fine-needle scan aspiration.showed pulmonary Neither BRAF metastases, nor NRAS which mutations were histologically were found inconfirmed the tumor by genomefine-needle analysis. aspiration. The patient Neither is currently BRAF nor treated NRAS with mutations anti-PD1 were immunotherapy. found in the tumor The first ge- PET-CTnome analysis. staging afterThe patient 3 months is currently showed a treated therapy with response anti-PD1 (smaller immunotherapy. pulmonary nodulesThe first andPET-CT no new staging lesions) after under 3 months ongoing showed therapy. a therapy response (smaller pulmonary nodules and no new lesions) under ongoing therapy.
FigureFigure 2. 2.Collision Collision tumor tumor consisting consisting of of keratoacanthoma keratoacanthoma and and melanoma, melanoma, Hematoxylin Hematoxylin and and Eosin Eosin stain (H&E). The small insert on the upper right side shows the edge of the keratoacanthoma with stain (H&E). The small insert on the upper right side shows the edge of the keratoacanthoma with characteristic architecture and large pale keratinocytes. characteristic architecture and large pale keratinocytes.
2.2. Discussion Discussion CollisionCollision tumorstumors consisting of of melanoma melanoma and and squamous squamous cell cell carcinoma carcinoma (called (called mel- melanocarcinomaanocarcinoma in the in literature) the literature) are very are rare, very and rare, their and biological their biological potential potential is unknown is un- [1]. knownVarious [1 theories]. Various try theoriesto explain try their to explain occurrenc theire: as occurrence: most collision as most tumors collision occur tumorson sun- occurdamaged on sun-damaged and aged skin, and the aged cancerization skin, the cancerization theory favors theory the development favors the development of two inter- ofmingled two intermingled neoplasms neoplasmsfrom two phenotypically from two phenotypically distinct clones distinct [2,3]. clones Paracrine [2,3]. stimulation Paracrine stimulationas a reason asfor a the reason development for the development of two different of two malignancies different malignancies at the same atsite the is samediscussed, site isbut discussed, their simultaneous but their simultaneous appearance appearancecould also just could be a also coincidence, just be a coincidence, as stated by asthe stated tumor bydivergent the tumor theory divergent [3–5]. theory In this [3 theory,–5]. In thisthe theory,neoplastic the neoplasticcells arise independently cells arise independently before col- beforeliding colliding[3]. On the [ 3other]. On hand, the other the so-called hand, thetumor so-called convergent tumor theory convergent explains theory the development explains theof collision development tumors of through collision multipotent tumors through stem cells multipotent undergoing stem dual cellsdifferentiation undergoing [3,6,7]. dual differentiationAlthough [ 3no,6, 7theory]. has to date been confirmed [3], collision tumors can be histolog- ically subdivided into an adjacent or intermingled growth pattern [8]. Some authors have
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Although no theory has to date been confirmed [3], collision tumors can be histo- logically subdivided into an adjacent or intermingled growth pattern [8]. Some authors have describeddescribed melanomas melanomas within seborrheic within seborrheic keratoses keratoses or in combination or in combination with basal with cell basal cell carci- carcinomas [5,7,nomas9]. Kochoumian [5,7,9]. Kochoumian et al. also report et al. aalso case report of metastatic a case of melanoma metastatic in melanoma collision in collision with squamouswith cell carcinomasquamous cell [1]. carcinoma The squamo-melanocytic [1]. The squamo-melanocytic tumor was described tumor was as adescribed as a mostly dermalmostly nodule dermal with intimately nodule with admixed intimately melanoma admixed and melanoma clear-cut squamousand clear-cut cell squamous cell carcinoma [10].carcinoma [10]. In our case, theIn overall our case, histological the overall picture histological showed pict anure invaginating showed an squamousinvaginating pro- squamous pro- liferation consistentliferation with consistent keratoacanthoma/well-differentiated with keratoacanthoma/well-differentiated squamous cell squamous carcinoma, cell carcinoma, keratoacanthomakeratoacanthoma type (Figure2). type This (Figure squamous 2). This lesion squamous exhibited lesion characteristic exhibited lipping characteristic of lipping of the edges, largethe pale edges, keratinocytes, large pale andkeratinocytes, micro abscesses and micr in epithelialo abscesses nests in epithelial at the bottom nests at the bottom (Figures2 and3).(Figures However, 2 and a conspicuous3). However, diffuse a conspicuous spindle celldiffuse proliferation spindle cell expressing proliferation expressing β high molecularhigh weight molecular cytokeratin weight (clone cytokeratin 34 E12) with(clone interspersed 34βE12) with islands interspersed of more differ-islands of more dif- entiated atypicalferentiated squamous atypical epithelium squamous suggested epithelium transition suggested into poorly/undifferentiated transition into poorly/undifferenti- squamous cell carcinomaated squamous (Figure cell4). carcinoma Further examination (Figure 4). Further of the epidermis examination adjacent of the to epidermis the adjacent tumor revealedto a junctionalthe tumor spindlerevealed cell a junctional proliferation spindle suspicious cell proliferation of melanoma suspicious in situ and of melanoma in a few solar lentiginessitu and further a few awaysolar lentigines from the tumor.further Subsequentaway from the immunohistochemical tumor. Subsequent immunohisto- analysis not onlychemical confirmed analysis the melanomanot only confirmed in situ but the also mela showednoma in positive situ but melanocyticalso showed positive mel- markers (Melan-A,anocytic HMB45, markers SOX10, (Melan-A, S100) HMB45, in the invasive SOX10, S100) spindle in the cell invasive component spindle of thecell component of β tumor (Figure5),the whereas tumor (Figure epithelial 5), whereas markers epithelial (AE1/3, 34 markersE12) were(AE1/3, negative. 34βE12) were negative.
Figure 3. DetailFigure of the 3. invasion Detail of front: the invasion Large palefront: keratinocytes Large pale keratinocytes and epithelial and nestsepithelial with nests micro with micro abscesses in a background of spindle-shaped melanoma cells (H&E stain). abscesses in a background of spindle-shaped melanoma cells (H&E stain).
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Figure 4. High molecularFigure 4. weightHigh molecular cytokeratin weight (clone cytokeratin 34βE12) stain (clone highlighting 34βE12) stain the epithelial highlighting compo- the epithelial Figure 4. High componentmolecular weight of the collisioncytokeratin tumor. (clone 34βE12) stain highlighting the epithelial nent of the collision tumor. component of the collision tumor.
Figure 5. Melan-A immunohistochemical stain highlighting the melanoma component of the FigureFigure 5. 5.Melan-A Melan-Acollision immunohistochemical immunohistochemical tumor. stain stain highlighting highlighting the the melanoma melanoma component component of theof the collision collision tumor. tumor. 3. Conclusions 3.3. Conclusions Conclusions Our report emphasizes the importance of timely tumor excision and thorough histo- OurOur report reportlogical emphasizes emphasizes examination, the the importance importance even in lesions ofof timelytimely that tumortumor are clinically excisionexcision unsuspicious and thorough and histo- appear to follow logicallogical examination, examination,an indolent even even in incourse. lesions lesions that that are are clinically clinically unsuspiciousunsuspicious andand appearappear to follow anan indolent indolent course. course. Author Contributions: Conceptualization, M.W.; software, M.W. and S.L.; validation, M.W., S.F. and AuthorAuthor Contributions: Contributions:S.L.; formal Conceptualization,Conceptualization, analysis, M.W.; M.W.; M.W.;investigation, so software,ftware, M.W, M.W. M.W. S.F. and and and S.L.; S.L.; S.L.; validation, validation, resources, M.W., M.W.; M.W., S.F. data S.F. and andcuration, M.W., S.F. S.L.;S.L.; formal formal analysis, analysis,and M.W.;S.L.; writing—original investigation, M.W, M.W., draft S.F. preparation, S.F. and and S.L.; S.L.; resources, M.W., resources, S.F. M.W.; and M.W.; S.L.; data writing—review data curation, curation, M.W., M.W., andS.F. editing, M.W., S.F.and and S.L.; S.L.; writing—original writing—originalS.F. and S.L.; draft visualization, draft preparation, preparation, M.W. M.W., and M.W.,S.F. S.L.; and S.F.supervision, S.L.; and writing—review S.L.; S.L.; writing—review project and administration, editing, and M.W., editing, M.W. All authors M.W.,S.F. and S.F. S.L.; and visualization, S.L.;have visualization, read M.W.and agreed and M.W. S.L.; to and supervision,the S.L.; published supervision, S.L.; version project S.L.; of administration, the project manuscript. administration, M.W. All Allauthors authors M.W. have All seen and ap- authorshave read have and read agreedproved and agreed to the the final published to the version published version of the version manuscriptof the manuscript. of the and manuscript. have All contributed authors All authors have significantly seen have and seen ap- to and the work. proved the final version of the manuscript and have contributed significantly to the work. approved the finalFunding: version ofThis the research manuscript received and no have external contributed funding. significantly to the work. Funding:Funding:This This research research received received no no external external funding. funding.
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Institutional Review Board Statement: Ethical review and approval were waived for this study, due to only one case report. Research was conducted ethically in accordance with the World Medical Association Declaration of Helsinki. Informed Consent Statement: The patient in this manuscript has given written informed consent to the publication of her case details. Acknowledgments: We would like to thank the patient for her contribution to the publication. Conflicts of Interest: The authors declare no conflict of interest.
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