Aimilios Lallas,1 Elvira Moscarella,1 Giuseppe Argenziano,1 Caterina Longo,1 Zoe Apalla,5
Gerardo Ferrara,4 Simonetta Piana,2 Simonetta Rosato3 and Iris Zalaudek1,6
1Skin Cancer Unit, 2Pathology Unit, 3Clinical Genetics Unit, Ostetric and pediatric Department, ArcispedaleSanta Maria Nuova IRCCS, Reggio Emilia, 4Anatomic Pathology Unit, Department of Oncology, GaetanoRummo General Hospital, Benevento, Italy, 5State Clinic of Dermatology, Hospital of Skin and Venereal
Diseases, Thessaloniki, Greece; and 6Department of Dermatology, Medical University of Graz, Graz, Austria
INTRODUCTION
There is mounting evidence that dermoscopy significantlyimproves the clinical diagnosis of most skin tumours and inconsequence, dermoscopy is nowadays an integral part ofthe clinical skin examination.1–3 The dermoscopic patternsof most common skin tumours, including melanocyticnaevi, seborrhoeic keratoses, dermatofibromas, vasculartumours, melanomas, basal cell carcinomas (BCC) andsquamous cell carcinomas (SCC) are well defined andestablished in everyday practice.4–6 However, a range ofuncommon skin tumours exists and their dermoscopic pat-terns have been described only sporadically. Here weprovide a review of the literature on the dermoscopic pat-terns of uncommon skin tumours along with representativeexamples from our database.
METHODS
In this retrospective study we searched our database forclinical and dermoscopic images of histopathologicallydiagnosed rare skin tumours using the following keywords:Merkel cell carcinoma (MCC), mesenchymal tumour,adnexal tumour and fibrous tissue tumour. Tumours diag-nosed as any type of melanocytic naevus, melanoma,seborrhoeic keratosis, haemangioma, angiokeratoma, pyo-genic granuloma, dermatofibroma, BCC and SCC wereexcluded. All dermoscopic images were evaluated by twodermatologists (AL and EM) in consensus for the presenceof specific morphological patterns. The dermoscopic crite-ria included: (i) vascular pattern (morphology and distribu-tion of vessels), (ii) background colour, (iii) pigmentation
structures and (iv) additional structures. If a disagreementarose between both evaluators the criterion was judged asbeing absent. A review of the literature was performedon PubMed Central with the keywords ‘dermoscopy’,‘dermatoscopy’ and the name of each tumour.
RESULTS
A total of 85 rare skin tumours with 26 differenthistopathological diagnoses meeting the search criteriawere extracted from our database (Table 1). The outcomeof the literature search included 48 studies describingdermoscopic criteria of 20 different entities (Table 1). Com-bining the results of our analysis and previously publisheddata, in Tables 2 and 3 we summarise the dermoscopic cri-teria of 26 uncommon skin tumours.
DISCUSSION
Rare skin tumours may escape clinical diagnosis, since theyare not at the frontline of a clinician’s differential diagnosisspectrum. Moreover, their clinical presentation is oftenunspecific, impeding their discrimination from othercommon entities. Dermoscopy may aid the clinical diagno-sis of rare skin tumours by displaying unusual criteria thatdo not match the well-defined patterns of most commonskin tumours.
Correspondence: Dr Aimilios Lallas, Skin Cancer Unit,Arcispedale Santa Maria Nuova, Viale Risorgimento 80, 42100,Reggio Emilia, Italy. Email: [email protected]
Conflict of interest: none.Aimilios Lallas, MD. Elvira Moscarella, MD. Giuseppe
The incidence of MCC has tripled in recent years and istoday estimated about 0.24 per 100 000 person-years.49–51
MCC shows a predilection for elderly white men and immu-nosuppressed patients.
MCC is a very aggressive carcinoma, associated with ahigh risk of locoregional and distant spread and poor sur-vival and, effectively, its early detection and wide local exci-sion are mandatory. Clinically, MCC most commonlydevelops as a persistent, asymptomatic, red or pink nodulethat rapidly increases in size over a period of weeks tomonths (Fig. 1). The most common sites of presentation arethe head and neck region and extremities, followed by thetrunk and oral and genital mucosa.49 Because of its unspe-cific clinical presentation, the differential diagnostic spec-trum of MCC is broad, including common malignanttumours (BCC, SCC, melanomas) and benign lesions suchas dermatofibroma or haemangioma.7–10 Diagnosis is oftendelayed, since more than half of MCC are thought to bebenign at the time of biopsy.
Dermoscopy of MCC typically reveals a milky red back-ground and a polymorphous vascular pattern, comprisingdotted, arborising, linear irregular and glomerular vessels(Fig. 1). Less often, milky red areas are combined with only
one morphological type of vessels, usually linear irregular.This dermoscopic pattern cannot be considered specific,since similar findings characterise amelanotic melanomaand other malignant tumours. However, dermoscopy mayenhance the discrimination between MCC and benigntumours by revealing features predictive of malignancy.Specifically, milky red areas, which represent the common-est criterion of MCC, are very rarely present in benignlesions (with the exception of pyogenic granulomas),whereas they are frequently detected in amelanotic mela-nomas. Additionally, the synchronous presence of morethan one morphological type of vessel (forming theso-called polymorphous vascular pattern) is also suggestiveof a malignant tumour, such as melanoma or SCC. Effec-tively, detection of one or both of the above phenomenashould warrant complete surgical excision. The latter isparticularly relevant in clinical practice, helping cliniciansto avoid diagnostic delay with undesirable consequences forthe patient.7,9
Cutaneous angiosarcoma
Cutaneous angiosarcoma is an aggressive neoplasm that isgenerally divided into three clinical variants: angiosarcomaof the head and scalp (AS), mainly affecting elderly men;lymphoedema-associated angiosarcoma (LAS) arising typi-cally in the context of Stewart–Treves syndrome andradiation-induced angiosarcoma (RIA) arising in previouslyirradiated skin areas.52 Recently, epithelioid angiosarcoma
Table 1 Histopathological diagnoses of tumours in our series andresults of the literature search
TumourNo of casesin our series
No of casespublished
Merkel cell carcinoma7–10 6 23Angiosarcoma11,12
Angiosarcoma of the head and scalp 3 9Radiation-induced angiosarcoma 0 4
has been described, as a rare, aggressive variant.53 Theclassic AS is characterised by a tendency to metastasize toregional lymph nodes and lungs, often after repeated sur-gical excisions of the primary growth. Prognosis is poor,with a 5-year survival rate of 12–33%.52 Surgical resectionrepresents the treatment of choice, but its application maybe limited by the wide extension of the tumour. Alterna-tively, AS might respond to a combined treatment consistingof chemotherapy prior to irradiation of the tumour field.
From a clinical point of view, early AS lesions develop asill-defined violaceous to bluish areas with an induratedborder. At this stage, the disease has to be discriminatedfrom bruising, rosacea, tumid lupus erythematosus or infec-tions such as erysipelas and cellulitis. Diagnosis of AS isoften suspected at advanced stages when lesions becomeelevated or nodular and occasionally ulcerated (Fig. 2).
Table 3 Dermoscopic characteristics of adnexal tumours
Tumour Dermoscopic criteria
Sebaceous cyst White/yellow central structureYellowish backgroundPeripheral telangiectasias (crown vessels)
Sebaceous hyperplasia White polylobular central structuresWhite structureless centreCentral umbilication (bonbon toffee sign)Peripheral telangiectasias (crown vessels)
Sebaceous adenoma Central opaque whitish structureYellowish backgroundPeripheral telangiectasias (crown vessels)
Sebaceoma Homogenous yellowish central structurePeripheral telangiectasias (crown vessels)
Figure 1 Clinical and dermoscopic image of a Merkel cell carci-noma arising on the right leg of a 60-year-old man. Dermoscopyrevealed milky red areas and irregular linear vessels.
Figure 2 Angiosarcoma of the scalp. Clinical image showing themultifocal presentation of an AS in a 70-year-old man. Dermoscopyof a nodular area revealed purple-blue colour and whitish lines.
Extensive local growth is common, and margins are difficultto define surgically. In approximately half of the patients thedisease manifests with multiple separate foci.
RIA and LAS tend to present as reddish to purple plaqueswith ill-defined borders.
On dermoscopy, the classic AS is characterised by combi-nations of the typical colours of vascular tumours, namelyred, purple and blue (Fig. 2). At the nodular part, white linescorresponding histopathologically to fibrous septa betweenenlarged neoplastic vascular spaces can be detected. RIA,instead, has been reported to exhibit a more homogeneouspinkish-white pattern.11,12,54
Tumours of the fibrous tissue
Atypical fibroxanthoma (AFX) and malignant fibroushistiocytoma (MFH) are related tumours with similarhistopathological characteristics, but they differ signifi-
cantly in their prognosis. The former, despite its tendency torecur after incomplete excision, has excellent prognosis,whereas MFH possesses a considerable metastatic poten-tial, being associated with an overall survival rate of50%.55–57
AFX occurs mainly on the sun-exposed parts of elderlyindividuals. Clinically, it manifests as a rapidly enlarging,reddish, dome-shaped nodule, often with an eroded orcrusted surface (Fig. 3a). Less often the tumour acquires adarker hue due to haemosiderin deposition. The clinicaldifferential diagnosis includes melanoma, BCC, SCC anddermatofibrosarcoma protuberans (DFSP).56 Dermosco-pically, AFX displays reddish and whitish areas in combina-tion with a polymorphous vascular pattern consisting ofvarious combinations of linear, dotted, hairpin and highlytortuous vessel irregularly distributed over the surface ofthe lesion.14 Ulceration, crusting and keratin masses mayalso be detected (Fig. 3b).
Figure 3 (a) Atypical fibroxanthoma presenting as a rapidly growing reddish nodule on the scalp of a 68-year-old man. (b) Dermoscopyrevealed reddish and whitish structureless areas, white/yellow crusts and a polymorphous vascular pattern consisting of dotted and thinirregular linear vessels in an asymmetric arrangement. (c) This bulky, ulcerated mass acquired this size in less than a year and washistopathologically diagnosed as malignant fibrous histiocytoma. (d) Dermoscopy revealed a highly polymorphous vascular pattern com-prising dotted, short linear and thick linear irregular vessels, in combination with ulceration and haemorrhage.
MFH develops as an enlarging subcutaneous nodule thatmay acquire significant size and ulcerate (Fig. 3c).57 Asshown in Fig. 3d, dermoscopy reveals a polymorphous vas-cular pattern comprising dotted, short, fine linear and thickirregular linear vessels, in combination with ulceration andhaemorrhage. Like MCC, although findings of AFX andMFH cannot be regarded as specific, dermoscopy minimisesthe risk of evaluating the tumour as benign. Specifically,detection of a polymorphous vascular pattern should raisesuspicion of a malignant tumour, warranting complete sur-gical excision.
DFSP is a relatively uncommon soft tissue neoplasm,characterised by a low-to-intermediate malignant potential.Analytically, although DFSP rarely metastasizes it is charac-terised by a locally aggressive biological behaviour and ahigh recurrence rate. Clinically, it initially presents as oneor multiple firm erythematous nodules or plaques that maysuppurate or ulcerate (Fig. 4a,c). At this stage, DFSP has tobe differentiated from dermatofibroma. The primary lesionsgradually enlarge and become confluent, forming charac-
teristic bulky, protuberant neoplastic masses. Dermoscopymight facilitate the clinical recognition of early lesions byrevealing a reddish background colour in conjunction withfine linear vessels (Fig. 4b,d).58 Although the dermoscopiccriteria of dermatofibroma have been extensively investi-gated, a similar pattern has not been reported up to date.59 Adelicate pigment network has also been described in DFSPbut it lacks the characteristic peripheral arrangementobserved in dermatofibroma.58
Adnexal tumours
Adnexal tumours are classified according to their adnexaldifferentiation as follicular, sebaceous, eccrine and apo-crine.60,61 Their natural course is generally favourable,although for several benign adnexal tumours a malignantcounterpart has also been described. Adnexal carcinomasare associated with a poor prognosis, which is, at leastpartially, related to their delayed recognition. Our seriesof tumours included two sebaceous carcinomas, one
Figure 4 (a,c) Two cases of early dermatofibrosarcoma protuberans, presenting as a solitary nodule. (b,d) Dermoscopy of the two tumoursmade similar findings, namely a reddish background colour in conjunction with fine linear vessels, distributed all over the surface of thelesion.
trichilemmal carcinoma and one porocarcinoma (Fig. 5). Asshown in Table 3, almost all malignant adnexal tumoursdescribed in the present and previous studies der-moscopically exhibit at least one feature suggestive ofmalignancy, most commonly a polymorphous vascularpattern.
Sebaceous tumours
Although consistent criteria for the diagnosis and nomen-clature of sebaceous tumours are lacking, these tumoursare traditionally classified as benign sebaceous hyperplasia,sebaceous adenoma, sebaceoma (sebaceous epithelioma)and sebaceous carcinoma. Apart from sebaceous cysts andsebaceous hyperplasia which are common entities, seba-ceous tumours are generally rare and typically occur in thecontext of Muir–Torre syndrome.62,63
Sebaceous hyperplasia is dermoscopically typified by awhitish umbilicated, polylobular or structureless centre,
surrounded by elongated, scarcely branching vessels(crown vessels). A similar pattern consisting of centralwhitish/yellowish structures and crown vessels character-ises sebaceous cysts.
Two main dermoscopic patterns of sebaceous adenomaand sebaceoma have been described. First, tumours with acentral crater, dermoscopically characterised by elongatedradial telangiectasias (crown vessels) surrounding anopaque, structureless ovoid white-yellow centre, which is attimes covered by blood crusts. Second, tumours withouta central crater, which reveal dermoscopically branchingbut unfocused arborising vessels over a white to yellowbackground and few loosely arranged yellow comedo-likeglobules.22 The combination of yellowish structures withunfocused arborising vessels is suggestive of the diagnosisof a sebaceous tumour. Differentiating among sebaceoustumours is troublesome, not only clinically but often alsohistopathologically. Our own and previous results demon-strate that this similarity is reflected also in the dermoscopic
Figure 5 (a) A sebaceous carcinoma developing on the thigh of a 50-year-old man. (b) Dermoscopy revealed a polymorphous vascularpattern comprising linear irregular and tortuous vessels, associated with yellowish structures and ulceration. (c) A trichilemma carcinomagradually enlarging on the scalp of a 65-year old man for almost 1 year. (d) Dermoscopy revealed a polymorphous vascular pattern, consistingof dotted, linear irregular and tortuous vessels, in conjunction with white-yellowish well-circumscribed areas and ulceration.
patterns of these entities (Fig. 5a,b). Dermoscopy enablestheir differentiation from sebaceous hyperplasia, which isa common entity, in contrast to the remaining sebaceoustumours, which appear almost exclusively in the context ofMuir–Torre syndrome.
Tumours of the hair follicle
In general, the dermoscopic pattern of follicular tumoursdisplays features overlapping with BCC, namely linearbranching vessels and blue-grey dots or globules.64 Thecommon presence of ‘white structures’ has been suggestedas a dermoscopic clue, suggestive of the diagnosis of afollicular tumour (Fig. 6). Specific dermoscopic criteriahave are associated with some tumours, such as the uniqueivory-white background colour that typifies desmoplastictrichoepithelioma (Table 3). A whitish colour can be alsodetected in morpheaform BCC, but it has a rather scar-like,instead of ivory, hue. Furthermore, morpheaform BCC
clinically presents as a flat or depressed firm lesion, unliketrichoblastoma and nodular BCC.
Pilomatricoma or calcifying epithelioma of Malherbe rep-resents the commonest follicular tumour, usually affectingchildren and adolescents.60 Irregular white and/or yellowstructures, white streaks, reddish homogenous areas andlinear vessels represent the most frequent dermoscopic cri-teria of pilomatricoma, while ulceration and blue-greyareas are common additional findings.29,30 The white struc-tures, histopathologically corresponding to calcification orkeratin masses, represent the most useful single criterionfor differentiating between pilomatricoma and malignanttumours, such as melanoma and BCC.
Sweat gland tumours
Eccrine poroma is the most extensively studied sweat glandtumour, concerning its dermoscopic pattern. It is character-ised by a high degree of dermoscopic variability, which
Figure 6 (a) Clinically, a trichilemma carcinoma usually presents as a verrucous lesion, whereas dermoscopy reveals keratin masses andperivascular whitish haloes. (b) Dermoscopy of a trichoblastoma revealing findings similar to basal cell carcinoma, namely arborising vesselsand a blue-grey nest. (c) Dermoscopy of desmoplastic trichoepithelioma reveals a unique ivory-white background colour. (d) Dermoscopyof pilomatricoma reveals irregular white or yellow structures, while linear irregular vessels and ulceration may be also present.
is possibly explained by the existence of distinct histo-pathological subtypes, depending on the location of thebasaloid aggregations in relation to the epidermis. Analyti-cally, eccrine poroma may display dermoscopically overlap-ping features with BCC, such as arborising vessels andblue-grey nests, but more often it exhibits a polymorphousvascular pattern or perivascular whitish haloes, mimickingamelanotic melanoma or keratinising tumours, respectively(Fig. 7).39–45
Mucinous carcinoma is characterised by eccrine sweatgland differentiation and represents a low-grade malignanttumour with the potential of local recurrence.61 Dermoscopyof mucinous carcinoma has been reported to mirror itspeculiar histopathology, revealing a whitish network andlight-brown globules, which histopathologically correspondto fibrous septum and mucinous deposition, respectively.48
A limitation of our study, as well as of all previous studiesreviewed here, is related to their design. Specifically, theywere descriptive morphological studies without a controlgroup and the accuracy of the proposed dermoscopic crite-ria cannot be assessed. Another limitation is the variabilityin definition of dermoscopic features among differentstudies. Although we attempted to use uniform terminologyfor the cases described in the current study, we cannot ruleout the possibility that in previous studies different termshave been used to describe the same dermoscopic feature,or that some investigators ignored criteria that othersincluded and vice versa.
In conclusion, our results, along with pre-existing evi-dence, show that dermoscopy, by providing additionalmorphological information, might enhance the clinicaldiagnosis of uncommon skin tumours. Although benignadnexal tumours are dermoscopic mimickers of BCC, spe-cific clues such as the whitish structures of folliculartumours and the yellowish structures associated with thecrown vessels of sebaceous tumours might aid their recog-nition. A dermoscopic examination is particularly useful inthe context of clinically unspecific and biologically aggres-
sive entities, such as MCC, MFH and adnexal carcinomas,which can often escape clinical detection, with severe con-sequences. The latter aggressive entities dermoscopicallyexhibit criteria such as milky red areas or a polymorphousvascular pattern which, although not pathognomonic for aspecific diagnosis, are highly suggestive of a malignanttumour. Accordingly, the detection of one (or more)such feature should warrant surgical excision andhistopathological confirmation of the diagnosis. Validationof the value of dermoscopy in the diagnosis of uncommonskin tumours requires appropriately designed studies fordiagnostic accuracy.
ACKNOWLEDGEMENT
Study supported in part by the Italian Ministry of Health(RF-2010-2316524).
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