Scalp tumors - Wiley Online Library

CME Article Submitted: 28.10.2017 Accepted: 10.4.2018 Conflict of interest None.

DOI: 10.1111/ddg.13546

Scalp tumors

Christine Maria Prodinger, Josef Koller, Martin Laimer Department of Dermatology, Salzburg Regional Medical Center, Paracelsus Medical University, Salzburg, Austria Section Editor Prof. Dr. D. Nashan, Dortmund

Summary Tumors of the scalp are characterized by an impressively broad and heterogeneous clinical spectrum. They frequently exhibit site-specific features distinguishing them from their counterparts elsewhere on the skin. Although mostly benign, diagnosis and treatment of these lesions may pose a significant challenge due to impaired visibility (and thus delayed detection), anatomical circumstances, exposure to (exogenous) noxious agents, distinct histological features, as well as the often-advanced age of affected individuals. This is even more true for malignant tumors of the scalp, which are uncommon but associated with a poor prognosis. Adequate patient care therefore requires interdisciplinary management. Against this background, the present article addresses general principles and distinct features of the most important tumors of the scalp.

Introduction

Although the incidence of tumors arising on the scalp is increased compared to those occurring elsewhere on the skin, these neoplasms are fortunately predominantly benign.

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The scalp extends from the external occipital protuberance to the supraorbital margin. Anatomical characteristics include its stratified structure (consisting of epidermis, dermis, subcutis, epicranial aponeurosis and the adjacent periosteum and skull) and the closely arranged adnexa (sebaceous glands, hair follicles, eccrine and apocrine glands) that are surrounded by a dense network of blood vessels and lymphatics. Said characteristics form the structural basis for the remarkably broad range of tumor types that may arise in this particular region, including over a hundred different neoplasms, hamartomas, malformations and cysts, both benign and malignant. Morphologically, a distinction is made between keratinocytic and melanocytic tumors, adnexal tumors, neoplasms of hematopoietic and lymphatic tissue, soft tissue tumors as well as neural tumors [1]. The growth pattern of these tumors is significantly affected by the resistance to infi ltration caused by the scalp’s stratified structure. Given the site-specific vertical limitation created by the cranial bones, tumors therefore characteristically grow horizontally. Although the incidence of tumors arising on the scalp is increased compared to those occurring elsewhere on the skin, these neoplasms are fortunately predominantly benign. Cysts constitute over 50 % of benign scalp tumors and primarily include trichilemmal, epidermoid and dermoid cysts; the estimated prevalence in the Western population is roughly 20 % [2]. Not least because of the high density of sebaceous glands, the scalp is the most common site of trichilemmal cysts, accounting for approximately 80 % of such lesions. There are numerous other benign scalp tumors such as lipoma, fibroma, pilomatricoma (calcified cyst), seborrheic keratosis, nevi, hemangioma, warts and pseudolymphoma [3].

© 2018 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd. | JDDG | 1610-0379/2018/1606

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While only approximately 1–2 % of all scalp tumors are malignant, they comprise up to 13 % of all malignant cutaneous neoplasms.

While only approximately 1–2 % of all scalp tumors are malignant, they comprise up to 13 % of all malignant cutaneous neoplasms [4]. However, relevant epidemiologic data is sketchy. In one of the few more comprehensive studies, Chui et al. examined 398 Taiwanese patients with malignant scalp tumors. They found that, in terms of sheer frequency, basal cell carcinoma (41.2 %) and squamous cell carcinoma (16.6 %) were the most common lesions (as in our part of the world), with a peak incidence between 60 and 79 years, followed by metastases, adnexal tumors, angiosarcoma as well as lymphoma in decreasing order of prevalence [5]. Against this complex background, the present article is intended to provide a concise overview of general principles and distinct features of the most important scalp tumors, without claiming to be exhaustive. The interested reader is referred to relevant publications.

Special characteristics of scalp tumors Not only are scalp tumors characterized by an impressively broad and heterogeneous clinical spectrum, they frequently exhibit site-specific features that distinguish them from their counterparts elsewhere on the skin.

Not only are scalp tumors characterized by an impressively broad and heterogeneous clinical spectrum, they frequently exhibit site-specific features that distinguish them from their counterparts elsewhere on the skin (Table 1). Examples of these peculiarities will be discussed below.

Nonmelanoma skin cancer, predominantly basal cell carcinoma and squamous cell carcinoma, is the most common type of skin cancer among Caucasians, showing a continuously increasing incidence.

Nonmelanoma skin cancer, predominantly basal cell carcinoma and squamous cell carcinoma, is the most common type of skin cancer among Caucasians, showing a continuously increasing incidence. Overall, 2–18 % of basal cell carcinomas and 3–8 % of squamous cell carcinomas are located on the scalp [4, 6, 7 ]. In this particular location, both tumors are clinically characterized by a greater tendency for ulceration. Thus, they more frequently present as chronic, non-healing ulcer, compared to elsewhere on the skin. Partly because squamous cell carcinomas of the scalp are often diagnosed at an advanced stage (which usually correlates with tumor diameter and depth of invasion), this location may be considered an independent risk factor (along with degree of differentiation and evidence of perineural infi ltration) for invasiveness, increased risk of recurrence and therefore a more unfavorable prognosis. However, this is not yet reflected in current classifications, including the UICC (2009) and the AJCC (2011) classification [8–13]. Basal cell carcinomas, too, recur more often on the scalp. In rare cases, they may even infi ltrate the cranium and dura (estimated incidence 0.03 %), especially when neglected or in case of particularly advanced disease [14–17 ]. Compared to elsewhere on the skin, basal cell carcinomas of the scalp are more often nodular and also pigmented. Some cases therefore meet the clinical and dermoscopic criteria for a melanocytic lesion, which may render it difficult to distinguish them from melanoma. For example, dermoscopy of basal cell carcinomas in this location more often shows blue-gray ovoid nests, brown-black dots/globules, radial lines connecting to a common base, a blue-white veil and usually two or more melanocytic patterns at the same time [18, 19].

In this particular location, both tumors are clinically characterized by a greater tendency for ulceration. Thus, they more frequently present as chronic, non-healing ulcer, compared to elsewhere on the skin.

Nonmelanoma skin cancer

Melanocytic scalp tumors Similar to melanocytic nevi of special sites (acral, genital), there is an increased prevalence of histological features of dysplasia in scalp nevi.

Clinical subtypes of melanocytic scalp lesions include common, papillomatous, congenital, blue, atypical and eclipse nevi (with central hypopigmentation). Dermoscopy usually shows a globular and globular-reticular pattern and prominent perifollicular hypopigmentation. Similar to melanocytic nevi of special sites (acral,


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Table 1 Examples of site-specific characteristics of important scalp tumors. (↑ = increased occurrence). Epidemiology (percentage of benign and malignant scalp tumors)

Site-specific characteristics

Scalp tumors

Subtype

Benign (98–99 %)

Trichilemmal cyst

40 %

Lipoma

30 %

`

Melanocytic nevi

28 %

`

Note: sometimes difficult to distinguish from well-differentiated liposarcoma by fine needle aspiration or biopsy

↑ dysplastic features Dermoscopy: ↑ globular, globular-reticular pattern, perifollicular hypopigmentation ` ↑ blue nevi with GNA11 mutation (note: increased risk of malignant transformation) `

Malignant (1–2 %)

Basal cell carcinoma

41 %

↑ tendency for ulceration, recurrence ↑ nodular, pigmented subtype ` Dermoscopy: ↑ melanocytic pattern ` `

Squamous cell carcinoma

16 %

`

Metastases

12 %

`

Lymphoma

5%

`

↑ tendency for ulceration, invasion, recurrence

Alopecia neoplastica: hematogenous breast cancer metastases ` (histological) correlation with primary tumor essential for diagnosis Mycosis fungoides;, folliculotropic variant more common ` Cutaneous B-cell lymphomas show a predilection for the scalp ` Note: transcranial invasion of aggressive subtypes

Angiosarcoma

< 1 % of all scalp tumors ` Highly aggressive (invasive, recurrent) ` Note: clinically mimics hematoma, rosacea, erysipeloid, radiodermatitis

Melanoma

< 1 % of all scalp tumors ` ↑ tendency for ulceration, lymphovascular infiltration, local recurrence ` ↑ desmoplastic subtype ` ↑ Breslow thickness (mean: 2.4 mm ± 1.66)

Adnexal carcinoma

< 1 % of all scalp tumors ` ↑ invasiveness ` ↑ lymphovascular infiltration

Merkel cell carcinoma

< 1 % of all scalp tumors ` ↑ invasiveness

genital), there is an increased prevalence of histological features of dysplasia in scalp nevi [20]. Blue nevi, which usually present as flat, blue-gray to blue-black pigmented lesions with a diameter of less than one centimeter, can grow to a size of several centimeters, especially the cellular variant. They are marked by an increased risk of malignant transformation, especially when there are mutations in the GNAQ and GNA11 gene. GNA11-mutated blue nevi – similar to blue nevus-associated

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Figure 1 70-year-old patient. Well-differentiated squamous cell carcinoma (ulcerated nodule; black arrow) in association with lentigo maligna melanoma (pigmented area; white arrow) on actinically damaged skin in the parietal region (a). Junctional proliferation of atypical melanocytes with prominent dendrites and solar elastosis, consistent with melanoma in situ (lentigo maligna type). In addition, there is scar tissue with focal evidence of squamous cell carcinoma (bottom right). (Immunohistochemical staining for S100, original magnification x 40) (b). Well-differentiated squamous cell carcinoma (black arrow) (hematoxylin-eosin stain, original magnification x 40) (c).

Blue nevi are marked by an increased risk of malignant transformation, especially when there are mutations in the GNAQ and GNA11 gene. GNA11-mutated blue nevi – similar to blue nevus-associated melanoma in general and melanoma mimicking cellular blue nevus – show a marked predilection for the scalp.

A more aggressive variant, desmoplastic melanoma, too, shows a predilection for the scalp (about 20 % of all cases).

melanoma in general and melanoma mimicking cellular blue nevus – show a marked predilection for the scalp [21]. Three to six percent of primary melanomas are located on the scalp. Men are more frequently affected. Common types include superficial spreading, nodular and lentigo maligna melanoma with a high mitotic rate (> 3/mm). A more aggressive variant, desmoplastic melanoma, too, shows a predilection for the scalp (about 20 % of all cases) [22] (Figure 1). On dermoscopy, pigmented lesions in this location are characterized in particular by areas of regression and diffuse hypopigmentation. Histologically, they exhibit an average (Breslow) thickness of 2.4 mm (± 1.66) and show a tendency for ulceration, lymphovascular infi ltration and local recurrence. At the same time, the rate of positive regional sentinel lymph nodes (SLNs) is lower; however, this may also be attributed to false-negative SLN fi ndings. Potential reasons for the latter may include site-specific methodical limitations (more frequent extracervical location of SLNs), the presence of multiple nuchal/cervical SLNs or inability to detect them due to diffuse lymphatic drainage. Patients with undetectable SLNs are known to have a poorer prognosis compared with SLN-positive patients [23–25]. Scalp melanoma, which accounts for 10 % of melanoma-related deaths, generally has a poorer prognosis than melanoma at other sites. Studies suggest that it is not just the location itself that is a risk factor. Rather, the clinical and pathological triad of tumor thickness, SLN involvement and ulceration, which is less favorable overall on the scalp, has a major impact on overall survival. Lymph node metastases (in the form of micrometastases without lymphadenopathy occurring in 30 % of all patients [26 ]), distant and, in particular, cerebral metastases are more common in patients with scalp melanoma [23, 24, 27–32].


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Tumors with predominant follicular differentiation

Tumors with predominant sebaceous differentiation

Table 2 Classification of the most important adnexal tumors based on their predominant histomorphological pattern (sebaceous vs. follicular differentiation [92]. Classification/characteristics

Examples

Benign tumors

Sebaceous adenoma

Malignant tumors

Extraocular sebaceous gland carcinoma

Mantleomas

Fibrofolliculoma

Cysts

Steatocystoma

Nonneoplastic / hamartomatous tumors

Sebaceous nevus

Ectopic sebaceous glands and related lesions Follicular germ cell differentiation


Biphasic epithelial-mesenchymal tumors with differentiation toward follicular germ cells and specific follicular stroma

Fibroepithelioma

Predominant matrix differentiation

Pilomatrixoma

Differentiation toward outer root sheath

Proliferating trichilemmal tumor

Infundibular differentiation

Trichoadenoma

Panfollicular differentiation

Fibrous papule

Follicular cysts

Trichilemmal cyst

Nonneoplastic/hamartomatous tumors

Basaloid follicular hyperplasia

Adnexal tumors Clinically, benign adnexal tumors usually present as firm, elastic, non-ulcerated, skin-colored or erythematous/ bluish and frequently hairless lesions of varying sizes (note: hair loss is an unfavorable sign). They typically remain asymptomatic for a long time and grow very slowly. On the other hand, rapid growth and ulceration, especially in elderly patients, raise the suspicion of malignancy or malignant transformation.

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Given that cutaneous adnexa are complex epithelial, myoepithelial and mesenchymal structures, the neoplasms originating therefrom are highly varied. Not surprisingly, about one in ten malignant scalp tumors is of adnexal origin [5]. They originate in hair follicles, sebaceous glands and more rarely in eccrine and apocrine sweat glands or their ducts. Thus, the histomorphological spectrum is broad. With the exception of eccrine glands, said structures originate from a common embryonic primordium, which not uncommonly leads to a single tumor exhibiting mixed differentiation (Table 2). Adnexal tumors can occur both sporadically and as part of rare genetic disorders such as Birt-Hogg-Dubé, Brooke-Spiegler, Cowden or Muir-Torre syndrome (Table 3). Early occurrence – starting at puberty – of multiple monomorphic lesions in particular corroborates the clinical suspicion of a predisposing syndrome. Sporadic cases usually manifest themselves in the 5th or 6th decade [33–36 ]. Clinically, benign adnexal tumors usually present as fi rm, elastic, non-ulcerated, skin-colored or erythematous/bluish and frequently hairless lesions of varying sizes (note: hair loss is an unfavorable sign). They typically remain asymptomatic for a long time and grow very slowly. On the other hand, rapid growth and ulceration, especially in elderly patients, raise the suspicion of malignancy or malignant transformation. In familial tumor syndromes, such alarm signs are often observed at a young age. A (predominantly) benign adnexal tumor with a marked predilection for the scalp, proliferating trichilemmal cyst (PTC) primarily affects older women. It usually presents as a solitary nodulocystic lesion, measuring 1–10 cm, and is thought to originate from a preexisting trichilemmal cyst. Histologically, it may


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Table 3 Examples of hereditary syndromes associated with a greater risk of developing scalp tumors [34, 93]. Syndrome

Associated scalp tumors

Other associated symptoms (selection)

Inheritance Mutations

Gorlin-Goltz syndrome


Skeletal anomalies, intracra- AR nial calcifications, keratocystic odontogenic tumors

Xeroderma pigmentosum

Squamous and basal cell carcinoma, melanoma (initial onset during childhood)

Photosensitivity, freckles, poikiloderma, CNS anomalies

AR

DDB2, ERCC2 (-5), XPA-G, XPV

Schimmelpenning syndrome

Extensive sebaceous nevus along Blaschko’s lines

CNS, ocular malformations, horseshoe kidney

Mosaic

HRAS, KRAS, NRAS

Phacomatosis pigmentokeratotica

Sebaceous nevus + (papular) nevus spilus along Blaschko’s lines

Vascular malformations, hemiatrophy, CNS anomalies

Mosaic

HRAS

Didymosis aplasticosebacea

Sebaceous nevus with aplasia cutis congenita

SCALP syndrome

Sebaceous nevus, congenital melanocytic giant nevus

Aplasia cutis, CNS anomalies

Brooke-Spiegler syndrome

Cylindroma, trichoepithelioma, milia, spiradenoma

Increased carcinoma risk

AD

CYLD

Familial cylindromatosis

Cylindroma, spiradenoma, trichoepithelioma


AD

CYLD

Cowden syndrome

Trichilemmoma

Mucosal fibromas, increased carcinoma risk, intestinal polyps

AD

PTEN

Birt-Hogg-Dubé syndrome Fibrofolliculoma (≥ 5 are pathognomonic), trichodiscoma, skin tags

Lung cysts, pneumothorax

AD

FLCN

Muir-Torre syndrome

Sebaceoma, sebaceous carcinoma, keratoacanthoma


AD

MSH2+1, SH6

Gardner syndrome

Infundibular cysts, hybrid cysts with matrix component, miliary osteoma cutis

Soft tissue fibromas, colorectal adenomas/ adenocarcinoma

AD

APC

Oldfield syndrome

Steatocystoma, trichilemmal cysts

Multiple colon polyps

Multiple pilomatricomas

Pilomatricoma

Myotonic dystrophy (Steinert’s disease)

Bazex-Dupré-Christol syndrome

Basal cell carcinoma, milia

Hypotrichosis, follicular atrophoderma

XD

BZX

Rombo syndrome

Basal cell carcinoma, trichoepithelioma

Atrophoderma vermicularis with follicular keratosis

AD

Costello syndrome

Syringoma

Woolly hair, cardiomyopathy, mental retardation

AD

PTCH1 + 2, SUFU

HRAS

Abbr.: AR, autosomal recessive; AD, autosomal dominant; XD, X-linked dominant.


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be difficult to make the distinction between PTC and squamous cell carcinoma as desmoplasia and/or proliferation of the epithelium into the cyst lumen may mimic pseudoinvasion. Trichilemmal keratinization, sharp demarcation, presence of a preexisting cyst and peripheral palisading are suggestive of PTC, whereas histological signs of malignancy include nuclear pleomorphism, increased mitotic activity, necrosis and ulceration [33, 35]. Virtually every benign adnexal tumor has a malignant counterpart. Though uncommon, given their aggressive local growth pattern and increased risk of lymph node (7.4 %) and distant metastasis (12.2 %), they are associated with a poor prognosis. The subgroup of malignant adnexal tumors has a 5-year overall and disease-specific survival rate of 73 % and 98 %, respectively [36–38]. Characterized by infi ltrative local growth, high recurrence yet low metastatic rates, primary cutaneous adenoid cystic carcinoma also has a predilection for the scalp. So does mucinous eccrine carcinoma, which primarily occurs in elderly individuals. The latter frequently presents as a soft, non-ulcerated nodule that tends to recur; it metastasizes in 15–20 % of all cases. Given their overlapping characteristics, it is often challenging to make an unequivocal clinical and histological distinction between (primary) malignant adnexal tumors of the scalp and cutaneous metastases (for example, sebaceous carcinoma versus a breast cancer metastasis with sebaceous differentiation) [35, 39, 40].

Compared with melanoma, this tumor – pathogenetically associated predominantly (> 80 %) both with UV radiation and with Merkel cell polyomavirus – is less common but has a higher mortality rate (> 15 %).

While, unlike melanoma, a tumor thickness of less than 10 mm correlates only slightly with clinical stage and rate of metastasis, the primary location on the scalp is a distinct risk factor for larger MCCs associated with distant metastasis (8.7 %), which reduces the median survival to nine months.

Merkel cell carcinoma The scalp is one of the predilection sites for Merkel cell carcinoma (MCC), too. Compared with melanoma, this tumor – pathogenetically associated predominantly (> 80 %) both with UV radiation and with Merkel cell polyomavirus – is less common but has a higher mortality rate (> 15 %). The embryonic origin of Merkel cells remains subject to controversial debate. Initially, they were thought to originate in the neural crest, which is why MCC used to be classified within the group of neuroendocrine tumors. Recent studies, however, point to an epidermal origin of these pale oval cells, which are located in the basal layer; the majority of Merkel cells are in close contact with sensory nerve endings [41]. Apart from ectodermal keratinocytes, it has also been suggested that mesodermal fibroblasts and even pre-/pro-B cells might be the origin of this tumor [42, 43]. While, unlike melanoma, a tumor thickness of less than 10 mm correlates only slightly with clinical stage and rate of metastasis, the primary location on the scalp is a distinct risk factor for larger MCCs associated with distant metastasis (8.7 %), which reduces the median survival to nine months. By comparison, the 5-year survival rate is 51 % for localized MCCs and 35 % in case of nodal involvement [44–46 ].

Lymphomas Even though the skin is (after the gastrointestinal tract) the second most common site of extranodal non-Hodgkin’s lymphoma (NHL) (estimated incidence in the skin 1 in 100,000), scalp lymphomas are very uncommon [47 ]. The most common B-cell lymphomas occurring on the scalp are primary cutaneous follicle center lymphoma and primary cutaneous marginal zone lymphoma, both of which have an excellent prognosis, with a 5-year survival rate of > 95 % and < 100 % respectively (Figures 2, 3). In rare cases, primary cutaneous diffuse large B-cell lymphoma can present as a painless, slowly growing scalp tumor, associated with a poor prognosis and a median survival of two to five years. Lymphoma cells can infiltrate the cancellous bone (of the skull) and spread via communicating veins into

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Figure 2 64-year-old patient. Asymptomatic, coalescing erythematous plaques on the forehead / around the hairline as well as in the left parietal region, some with central pseudovesicles; diagnosis: cutaneous follicle center lymphoma (a). Histology shows dense lymphocytic infiltration of the dermis and formation of germinal centers (CD-20 +, CD-21 +, bcl-6 +) (hematoxylin-eosin stain, original magnification x 40 (b). Colonization of germinal centers by bcl-2 positive cells from the mantle zone (insert).

Figure 3 Multifocal follicle center lymphoma on the scalp of a 69-year-old female patient, presenting as disseminated, rather subtle, asymptomatic violaceous plaques.


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Among T-cell lymphomas, mycosis fungoides (predominantly with large-cell transformation) is the most common type occurring on the scalp, not rarely in the form of the prognostically more unfavorable folliculotropic variant (follicular papules; with/without mucin).

the soft tissues on both sides of the cranium. Progressive intracranial expansion subsequently leads to headaches, neurological deficits and epileptic seizures [3, 48–50]. Among T-cell lymphomas, mycosis fungoides (predominantly with large-cell transformation) is the most common type occurring on the scalp, not rarely in the form of the prognostically more unfavorable folliculotropic variant (follicular papules; with/without mucin). Finally, primary cutaneous large-cell anaplastic lymphoma, with a good 10-year survival rate of approximately 90 %, also occurs in this region [51, 52].

Sarcomas Typical clinical features of this (usually sporadic) tumor are a highly aggressive course associated with a tendency for multifocal spread and early hematogenous dissemination. In the head region in particular, there is a high rate of local recurrences, even if the tumor was initially excised with wide (2–3 cm) surgical margins. It must also be borne in mind that the distinction between well-differentiated liposarcoma and lipoma using fine-needle aspiration or tissue biopsies may at times be challenging or even impossible.

Among the heterogeneous group of sarcomas, all of which are of mesenchymal origin, angiosarcoma in particular (1 % of all sarcomas) has a predilection for the scalp. Typical clinical features of this (usually sporadic) tumor are a highly aggressive course associated with a tendency for multifocal spread and early hematogenous dissemination. In the head region in particular, there is a high rate of local recurrences, even if the tumor was initially excised with wide (2–3 cm) surgical margins. Accordingly, the 5-year survival rate is only 10–30 %. Not infrequently is angiosarcoma initially diagnosed following a pneumothorax, which is due to its tendency for subpleural metastasis [53, 54]. There have also been reports of liposarcoma arising on the scalp, with the myxoid subtype being the most common variant. Rapid growth and potential tissue necrosis can make it difficult to distinguish such a lesion from an infected benign trichilemmal cyst. It must also be borne in mind that the distinction between well-differentiated liposarcoma and lipoma using fi ne-needle aspiration or tissue biopsies may at times be challenging or even impossible [55].

Metastases The scalp’s vascularity likely facilitates the relatively common occurrence of metastases in this region, predominantly from visceral tumors.

Histological assessment of metastases always requires correlation with the primary tumor, given that different tumor types – especially on the scalp – can show morphological and immunohistochemical overlap with metastases originating from tumors of other organ systems.

The scalp’s vascularity likely facilitates the relatively common occurrence of metastases in this region, predominantly from visceral tumors [56 ]. In women, over 70 % of metastases are attributable to breast cancer, followed by ovarian, lung, gastrointestinal and oropharyngeal cancer. In men, 10 % of metastases originate from the lung and gastrointestinal tract, followed (in decreasing frequency) by ENT/esophageal tumors and renal tumors [57 ]. Clinically, metastases typically present as highly indurated, indolent lesions. Alopecia neoplastica is a distinct, site-specific clinical presentation, which is usually caused by hematogenous breast cancer metastases. Tumor infi ltration and the inflammation associated therewith lead to the destruction of hair follicles, clinically characterized by hair loss, indurated skin and telangiectasia. Histological assessment of metastases always requires correlation with the primary tumor, given that different tumor types – especially on the scalp – can show morphological and immunohistochemical overlap with metastases originating from tumors of other organ systems [58].

Pediatric scalp tumors Lack of lesional mobility or a midline location should prompt an initial radiographic evaluation to rule out cranial (meningo-)encephalocele.

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Pediatric scalp tumors are relatively rare and fortunately mostly (> 98 %) benign. Tumorous scalp lesions in this age group therefore predominantly have no neoplastic origin (Table 4). In this context, lack of lesional mobility or a midline location should prompt an initial radiographic evaluation to rule out cranial (meningo-) encephalocele [59].


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Table 4 Differential diagnoses of (commonly benign) scalp tumors in children [94]. Congenital

Epidermal cyst, dermoid cyst, meningocele, encephalocele, craniosynostoses

Neoplastic – benign

Neurofibroma, osteoma, fibrous dysplasia, osteoid osteoma, ossifying fibroma, giant cell tumor, aneurysmal bone cyst, lymphangioma, meningioma

Neoplastic – malignant

Neuroblastoma, lymphoma, sarcoma (Ewing’s, osteogenic, meningeal), glioma

Posttraumatic

Scalp hematoma, traumatic leptomeningeal cyst, subgaleal hematoma, subdural hygroma

Vascular

Hemangioma, pericranial sinus, arteriovenous fistula/ cirsoid aneurysm

Inflammatory

Lymphadenopathy, abscesses, necrobiotic nodules, cranial fasciitis, osteomyelitis

Idiopathic

Langerhans cell histiocytosis, myofibromatosis, osteitis deformans (Paget’s disease)

With an incidence of 0.5–1 %, nevus sebaceus (NS) is among the most common benign scalp tumors in children. A complex hamartoma, NS is characterized – among other things – by sebaceous and sweat gland hyperplasia with absence of terminal hair follicles within the lesion. The lesion is caused by postzygotic mutations in the HRAS (95 % of cases) and KRAS genes (5 %), which also explains its linear arrangement along Blaschko’s lines (mosaic RASopathy). While only about 1.7 % of pediatric sebaceous nevi give rise to – largely benign – tumors, approximately 10–30 % of adult cases are associated with complications in the form of syringocystadenoma, trichoblastoma or trichilemmoma (Figure 4). Basal cell carcinoma (occurs in 3.5 % of all sebaceous nevi) and other malignant epithelial tumors such as malignant sebaceous gland carcinoma tend to be an exception in adults, too; female patients are predominantly affected [60]. Occasionally, sebaceous nevi

Figure 4 Sebaceous nevus of the left temple in a 23-year-old patient presenting as characteristic waxy reddish-yellow papules; there is a nodular basal cell carcinoma arising in the medial aspect of the lesion.


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are associated with various syndromes (including RASopathies) (Table 3). While prophylactic excision is not always necessary for the aforementioned reasons, prominent alopecia due to a sebaceous nevus may still be highly stigmatizing. Given the relatively small size of lesions during infancy, early surgical removal (usually associated with very good cosmetic outcomes) may therefore be considered in such cases [61].

Pathogenetic principles of scalp tumors UV exposure and reduced UV protection due to sparse hair (early childhood, [androgenetic] alopecia) or Fitzpatrick skin types I and II are considered the most important risk factors for developing (malignant) scalp tumors.

In addition, repeated contact with polycyclic hydrocarbons, chronic wounds, scars and human papillomaviruses (especially HPV types 16, 18 and 31) also promote the development of these malignant tumors.

There is a marked increase in the incidence of nonmelanoma skin cancer (NMSC) with age due to less effective immune surveillance; this also applies to immunosuppressed patients (including iatrogenic immunosuppression).

UV exposure and reduced UV protection due to sparse hair (early childhood, [androgenetic] alopecia) or Fitzpatrick skin types I and II are considered the most important risk factors for developing (malignant) scalp tumors. Gender-specific differences in average hair length and in the incidence and clinical pattern of (e.g., androgenetic) alopecia with resultant differences in the intensity of cumulative UV exposure of the scalp also have an impact with respect to typical gender-related predilection sites for scalp tumors. According to Chiu et al., the frontal and vertex region are affected in women in particular, whereas men, who are more exposed overall, frequently develop lesions on the temples and in the postauricular and occipital regions; malignant scalp tumors are four times more common in men [5]. In addition, repeated contact with polycyclic hydrocarbons, chronic wounds, scars and human papillomaviruses (especially HPV types 16, 18 and 31) also promote the development of these malignant tumors [4, 62, 63]. Previous radiation therapy in the scalp region is also associated with an increased risk of malignant tumors. For example, the relative risk of basal cell carcinoma in particular is increased 3.6-fold (95 % CI) for those patients who were exposed to a cumulative dose of 4.8 Gy during radiation therapy for tinea capitis, which was popular in the fi rst half of the last century. Moreover, 40 % patients thus treated exhibit a more unfavorable multifocal growth pattern [64]. There is a marked increase in the incidence of nonmelanoma skin cancer (NMSC) with age due to less effective immune surveillance; this also applies to immunosuppressed patients (including iatrogenic immunosuppression). For instance, about 70 % of Australian transplant recipients develop a squamous cell carcinoma within 20 years (Figure 5) [65]. In addition, there is an increased risk of infi ltrative growth and tumor dedifferentiation. Although the mutation profi le

Figure 5 Disseminated actinic keratoses (carcinoma in situ) with progression to poorly differentiated squamous cell carcinoma (G2; arrows) in the parietal region of an 82-year-old patient with a history of longstanding immunosuppression with azathioprine for Crohn’s disease.

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is heterogeneous overall, UV signature mutations in p53-, CDKN2A or Ras genes confi rm a direct correlation between UV exposure, DNA damage and skin carcinogenesis [13]. These kinds of mutations have been found in nonmelanoma skin cancer and atypical fibroxanthoma (AFX, dermal sarcoma). The latter is a rare mesenchymal tumor characterized by pseudosarcomatous proliferation of dermal fibroblasts. It has been classified as a superficial variant of (the more invasive and aggressive) pleomorphic dermal sarcoma [66 ]. Finally, photosensitizing genetic disorders and congenital DNA repair and immune defects (such as albinism, xeroderma pigmentosum) may predispose to a remarkably early occurrence of these epithelial malignancies [62].

Diagnosis Relatively frequently are scalp tumors diagnosed only at an advanced stage when they present as visible/palpable masses. Early detection is often rendered difficult because of the (dense) hair and the inaccessibility of certain regions to self-inspection. Tumors can therefore remain undetected for a prolonged period of time. In light of the astonishingly low rate of correct preoperative diagnoses as regards scalp tumors (13–27 %), indistinct and suspicious lesions should always warrant histological confirmation.

Non-neoplastic lesions must always be distinguished (Table 4, Figure 7), given that tumors/tumorous lesions of the scalp may not only originate in the skin but (as noted above, especially in children) may also indicate an underlying process of the cranium or point to craniocephalic malformations (“tip of the iceberg”).

Relatively frequently are scalp tumors diagnosed only at an advanced stage when they present as visible/palpable masses. Early detection is often rendered difficult because of the (dense) hair and the inaccessibility of certain regions to self-inspection. Tumors can therefore remain undetected for a prolonged period of time. For the same reasons, the patient’s own account with regard to duration and changes in color and shape is less reliable. This circumstance underscores the importance of regular and thorough scalp exams. In this context, special training programs for certain professions such as hairdressers appears useful. Given that hairdressers regularly inspect the scalp of a large part of the population, they can detect suspicious lesions and thus play a key role in early diagnosis [67 ]. Although most benign scalp tumors require surgical intervention only when they become inflamed or for cosmetic reasons, distinguishing them from malignant tumors purely on clinical grounds is often challenging or even impossible. In light of the astonishingly low rate of correct preoperative diagnoses as regards scalp tumors (13–27 %), indistinct and suspicious lesions should always warrant histological confi rmation [3]. For example, angiosarcoma can mimic numerous (more banal) skin conditions (hematoma, rosacea, erysipeloid, radiodermatitis) and should therefore always be considered in the differential diagnosis (Figure 6) [53]. With respect to the interpretation of clinical symptoms, it should be noted that even histomorphologically benign scalp tumors may pose a differential diagnostic challenge. Given the limited space for expansion in this region, they can lead to compression and (early) infi ltration/erosion of neighboring structures, with associated symptoms such as facial swelling and proptosis. Initial clinical symptoms may therefore be misleading. Noninvasive methods (such as dermoscopy and confocal laser microscopy) may also be useful in the (differential) diagnostic workup (as well as for follow-up, preoperative determination of tumor borders and assessment of excision margins) in the cosmetically delicate scalp region. Non-neoplastic lesions must always be distinguished (Table 4, Figure 7), given that tumors/tumorous lesions of the scalp may not only originate in the skin but (as noted above, especially in children) may also indicate an underlying process of the cranium or point to craniocephalic malformations (“tip of the iceberg”). Imaging studies such as ultrasound (index lesion, lymph nodes), CT (bone, lymph nodes), MRI (soft tissue, nerves) are important especially for large, hard immobile lesions, yet also for those with a midline location (e.g., subdural empyema, dermoid cyst). These tests help narrow down the differential diagnosis and determine the extent or depth of a given lesion (also during follow-up). Large congenital nevi (> 20 cm) and those associated with satellite nevi should be worked up for neurocutaneous melanocytosis (in 5–10 %) as soon as possible using cranial MRI,


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Figure 6 72-year-old patient. Indolent, rapidly growing, partly ulcerated, firm erythematous nodules in the left temporo-occipital region (hematoxylin-eosin stain, original magnification x 40) (a). Moderately differentiated angiosarcoma, showing diffuse infiltration by irregular aggregates of atypical endothelial cells intermingled with bizarre slit-like vascular structures (hematoxylin-eosin staining, original magnification x 200) (b, c).

Figure 7 A 57-year-old patient presenting with a sharply demarcated erosion (7 × 3 cm) in the central parietal region. In addition, there are smaller, sharply defined erosions on the right side of the scalp (within reach of the right hand). Diagnosis: artifact associated with psychiatric comorbidity.

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As regards the histological evaluation of scalp tumors, it should be borne in mind that non-mesenchymal lesions in this region frequently exhibit spindle-cell morphology (e.g., squamous cell carcinoma, [desmoplastic] melanoma) or pseudomalignant features; this phenomenon is artificially augmented in small, crushed biopsies. If there is evidence of malignancy, current guidelines recommend a complete diagnostic workup including clinical examination (thorough skin exam, palpation of lymphatic drainage pathways/ regional lymph nodes), imaging studies (ultrasound, CT/MRI, PET-CT) and possibly further biopsies, depending on the primary tumor type.

especially if there are neurological symptoms (signs of increased intracranial pressure) [68, 69]. As regards the histological evaluation of scalp tumors, it should be borne in mind that non-mesenchymal lesions in this region frequently exhibit spindle-cell morphology (e.g., squamous cell carcinoma, [desmoplastic] melanoma) or pseudomalignant features; this phenomenon is artificially augmented in small, crushed biopsies. Given these micromorphological peculiarities, shave biopsies should be avoided to ensure that the tissue sample is as representative as possible [70]. Reliable and representative assessment of adnexal tumors in particular frequently requires complete excision as these lesions can present considerable diagnostic problems due to their morphological variety and essential clinicopathological overlap (Table 2). If there is evidence of malignancy, current guidelines recommend a complete diagnostic workup including clinical examination (thorough skin exam, palpation of lymphatic drainage pathways/regional lymph nodes), imaging studies (ultrasound, CT/MRI, PET-CT) and possibly further biopsies, depending on the primary tumor type (see, for example, www.awmf.org, www.ado-homepage.de, www.eado.org, www.euroderm.org/edf ). The significance of sentinel lymph node biopsy (SLNB) for malignant scalp tumors remains unclear, not least because of the high rate of false-negative results (see above). Nevertheless, SLNB should be considered in the case of satellite and in-transit metastases and for melanomas with a Breslow thickness ≥ 0.8 mm [71–73].

Treatment principles Topical field therapy of early forms of nonmelanoma skin cancer For the treatment of superficial basal cell carcinoma, the aforementioned topical agents (with the exception of imiquimod and conventional photodynamic therapy) are only available for off-label use.

Considered to be noninvasive squamous cell carcinomas in situ, actinic keratoses are among the most common early forms of malignant scalp tumors in everyday clinical practice; one in three patients over the age of 30 (seen by a dermatologist) is affected [74]. As regards the therapeutic approach to actinic keratoses, it has proven useful to make a distinction between the treatment of individual lesions and field therapy; the latter is employed for multiple lesions or those with indistinct tumor borders. However, there is only limited qualitative evidence from studies comparing the effectiveness of the various treatment options available. In addition, response rates of 70–80 % contrast with high recurrence rates [75]. Given that certain one-time treatments are not sufficiently effective (depending on extent, site, tolerability and compliance, among other things), it is important that methods employed for a longer period of time have a low side effect profi le. One of the classic modalities used for destroying localized and hypertrophic actinic keratoses and superficial basal cell carcinomas is cryotherapy. A relatively time-efficient and inexpensive procedure, healing is often associated with hypopigmented scars [76 ]. Field therapy plays a significant role especially for prevention as it allows for subclinical and incipient in situ carcinomas to be treated, thus preventing potential progression to invasive cancer [9, 77, 78]. Therapeutic agents include imiquimod, 5-fluorouracil, diclofenac/hyaluronic acid and ingenol mebutate as well as conventional or daylight photodynamic therapy [75]. However, topical immunomodulators such as imiquimod may have a limited therapeutic effect in the scalp region, possibly because they cannot be applied as evenly due to the presence of hair [75, 79]. For the treatment of superficial basal cell carcinoma, the aforementioned topical agents (with the exception of imiquimod and conventional photodynamic therapy) are only available for off-label use; they should not be used for other basal cell carcinoma subtypes because of insufficient efficacy [75].


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Figure 8 Recommended surgical margins for the most common malignant skin tumors.

Primary excision In this context, for example, congenital nevi used to be surgically removed as soon as possible to reduce the allegedly increased melanoma risk. Today, however, a limited surgical approach is recommended.

Complete primary excision (with/without micrographic margin control), possibly followed by re-excision with tumor-specific surgical margins, is the treatment of choice for all malignant scalp tumors.

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Excision of benign lesions is sometimes indicated for cosmetic and psychosocial reasons, if they cannot be unequivocally distinguished from malignant lesions, or if they become symptomatic, for instance by compressing other structures. In this context, for example, congenital nevi used to be surgically removed as soon as possible to reduce the allegedly increased melanoma risk. Today, however, a limited surgical approach is recommended [80, 81]. Surgical removal of congenital nevi up to 20 cm in size may be considered between the ages of one and two if surgically feasible, and mainly for cosmetic reasons, given the low overall risk of malignant transformation (0.1 % for nevi up to 10 cm in diameter and 1 % for nevi 10–20 cm in size). In addition, congenital nevi of the scalp usually tend to become lighter over time and thus cosmetically less bothersome, even though the infi ltration persists. However, (serial partial) excision is defi nitely indicated for all irregular and otherwise suspicious scalp lesions (for example, thick, nonhomogeneous nodular nevi) as follow-up is more difficult because of the hair [80–82]. At any rate, surgical intervention is required if malignancy is clinically suspected or if there is deeper infi ltration or increased invasiveness (for example microcystic, sclerosing basal cell carcinoma). Clinical signs include induration, bleeding, increase in diameter, erythema, ulceration, hyperkeratosis, pruritus, pigmentation, pain). Complete primary excision (with/without micrographic margin control), possibly followed by re-excision with tumor-specific surgical margins, is the treatment of choice for all malignant scalp tumors[8, 15, 17, 83] (Figure 8). Following excision, “simple” primary defect closure is preferable to more complex fl ap repairs because of the higher complication rates and greater subsequent diffi culty in determining the excision margins if the primary excision was incomplete [84].


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Strategies for local tumor control Treatment options for inoperable tumors predominantly include radiation therapy and – increasingly – also electrochemotherapy. Using brief intense electric pulses, the latter involves the delivery of a chemotherapeutic agent such as bleomycin via electroporation directly into the (tumor) cells, where it achieves a high local concentration.

Treatment options for inoperable tumors predominantly include radiation therapy and – increasingly – also electrochemotherapy. Using brief intense electric pulses, the latter involves the delivery of a chemotherapeutic agent such as bleomycin via electroporation directly into the (tumor) cells, where it achieves a high local concentration. This method is suitable for all inoperable yet accessible skin tumors such as squamous cell carcinoma, cutaneous metastases, Merkel cell carcinoma and angiosarcoma [85, 86]. In addition, there is an approved oncolytic tumor vaccine available for the treatment of advanced melanoma, which exerts both local and systemic anti-tumor effects [87 ].

Systemic therapies Systemic treatment options for locally advanced and metastatic tumors include immunotherapies (for example, PD-1 inhibitors for melanoma and Merkel cell carcinoma) and targeted molecular therapies based on the genetic tumor profile.

Systemic treatment options for locally advanced and metastatic tumors include immunotherapies (for example, PD-1 inhibitors for melanoma and Merkel cell carcinoma) and targeted molecular therapies based on the genetic tumor profile. See current recommendations and guidelines issued by various scientific societies: www.awmf.org, www.ado-homepage.de, www.eado.org, www.euroderm.org/edf (Table 5). To some extent, the latter have become routinely available for certain tumors (for example, melanoma, basal cell carcinoma, dermatofibrosarcoma protuberans). Classic cytotoxic chemotherapies continue to be used, largely for palliation. Given the complexity of these tumors, which often require multidisciplinary expertise, treatment regimens should be agreed on in a quality-assured manner and always involve an interdisciplinary tumor board.

Prevention Irrespective of improvements and the increase in treatment options in recent years, preventive measures (UV avoidance [textile, chemical and physical UV protection], consistent follow-up for early detection of recurrence) continue to be critically important. Raising public awareness for this issue remains a key task of our specialty.

Prognosis Malignant scalp tumors are generally characterized by a more aggressive biological behavior than their counterparts at other sites. Basal cell and squamous cell carcinoma, angiosarcoma and dermatofibrosarcoma protuberans, as well as Merkel cell carcinoma, microcystic adnexal carcinoma, metastases, melanoma and, in children, rhabdomyosarcoma have considerable destructive potential and are associated with significant complications due to infi ltration/invasion of the periosteum, bone, dura and brain [17, 31, 88]. The risk of osseous infiltration correlates with disease duration and tumor size, prior therapies (radiation therapy) and (aggressive) histological growth pattern (for example, sclerosing, micronodular, metatypical basal cell carcinoma) [15, 89]. Factors that potentially have a negative effect on prognosis not only include the often-advanced age of the patients (comorbidities, “surgical resilience”), but also the inherently limited accessibility for surgery and radiation therapy. This is the reason why – in the scalp region – local tumor control is considered prognostically more signifi cant overall than the tumor-specifi c potential for metastasis [90, 91].


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x x

x

Merkel cell carcinoma

Lymphoma

Sarcoma

x

x

x

x

x

x

x*

x*

x*

x*

x*

x*

x*

Anti-PD-L1 Ab (avelumab)*

PDGFR- α inhibitor, tyrosine kinase inhibitor, VEGF inhibitor, endoglin Ab*, growth factor (VEGF), and others

x*

Fusion proteins, synthetic Interferon alpha retinoids, monoclonal Ab, histone deacetylase inhibitor, and others

Tyrosine kinase inhibitor (pazopanib)*

x

Anti-CTLA4 Ab (ipiBRAF, MEK inhibitor (dabrafenib, vemurafenib, limumab), anti-PD1 Ab (pembrolizumab, cobimetinib, trametinib) nivolumab), oncolytic virus T-VEC

x

x

x

x*

x*

x*

PUVA (psoralen + UVA), ECP, hematopoietic stem cell transplantation, and others

Somatostatin analogs*

Itraconazole*

Chemotherapy Other

EGFR inhibitor (cetuximab, Anti-PD1 Ab* panitumumab)

Hedgehog inhibitor (vismodegib, sonidegib)

Immunotherapy

*Limited data. Abbr.: Ab, antibody; T-VEC, talimogene laherparepvec; EGFR, epidermal growth factor receptor; PDGRF, platelet-derived growth factor; VEGF, vascular endothelial growth factor; ECP, extracorporeal photopheresis [95–97].

x

Adnexal tumors

x x

x

Squamous cell carcinoma

x

Melanoma

x

Topical Excision (with Radiation Electrochemotherapy Targeted therapy agents sufficient surgical margins)


Scalp tumors

Table 5 Overview of established and experimental therapies for the treatment of malignant scalp tumors

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Conclusion An interdisciplinary approach is desirable in the management of scalp tumors, given the complex and delicate location as well as the variety of clinical and morphological manifestations and the diagnostic and therapeutic challenges associated therewith. This must be emphasized all the more as independent care of patients with rare scalp tumors by various medical specialties (such as pediatrics, dermatology, plastic and neurosurgery, ENT or ophthalmology), which has been common practice, limits the generation of individual expertise and comprehensive data collection. However, such epidemiological data is necessary for reliable conclusions to be drawn about the incidence of these tumors and possible pathogenetic factors. References 1 2 3 4 5

6

7

8 9 10 11 12 13 14 15

Correspondence to

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Dr. med. univ. Christine Maria Prodinger Universitätsklinik für Dermatologie

17

Müllner Hauptstraße 48 5020 Salzburg, Austria E-mail: [email protected]

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Agur M, Lee MJ, Grant JC. Grant’s atlas of anatomy. 9th ed. Lippincott Williams & Wilkins, Baltimore, MD, 1991: 464 . Al-khateeb TH, Al-Masri NM, Al-Zoubi F. Cutaneous cysts of the head and neck. J Oral Maxillofac Surg 2009; 67: 52 –7. Türk CÇ , Bacanlı A , Kara NN. Incidence and clinical significance of lesions presenting as a scalp mass in adult patients. Acta Neurochir 2015; 157(2): 217–23. Anrade P et al. Epidemiology of basal cell carcinomas and squamous cell carcinomas in a Department of Dermatology: a 5 year review. An Bras Dermatol 2012; 87(2): 212 – 9. Chiu CS, Lin CY, Kuo TT et al. Malignant cutaneous tumors of the scalp: a study of demographic characteristics and histologic distributions of 398 Taiwanese patients. J Am Acad Dermatol 2007; 56( 3): 448 – 52. Ghanadan A , Abdollahi P, Rabet M et al. Different anatomical distribution of basal cell carcinoma subtypes in Iranian population: association between site and subtype. Ann Dermatol 2014; 26( 5): 559 – 63. Youl PH, Janda M, Aitken JF et al. Body-site distribution of skin cancer, pre-malignant and common benign pigmented lesions excised in general practice. Br J Dermatol 2011; 165(1): 35–43. Sobin LH, Gospodarowicz MK , Wittekind C. TNM Classification of malignant tumours (UICC International Union Against Cancer) (ed 7), John Wiley & Sons, 2009. Edge SB, Byrd DR , Compton CC et al. AJCC Cancer Staging Manual (ed 7). New York, Dordrecht, Heidelberg, London, Springer, 2009. Johnson TM, Rowe DE, Nelson BR , Swanson NA . Squamous cell carcinoma of the skin (excluding lip and oral mucosa). J Am Acad Dermatol 1992; 26: 467– 84 . Brodland DG, Zitelli JA . Mechanisms of metastasis. J Am Acad Dermatol 1992; 27: 1 – 8. Que SKT, Zwald FO, Schmults CD. Cutaneous squamous cell carcinoma: Incidence, risk factors, diagnosis, and staging. J Am Acad Dermatol 2018; 78(2): 237–47. Que SKT, Zwald FO, Schmults CD. Cutaneous squamous cell carcinoma: Management of advanced and high-stage tumors. J Am Acad Dermatol 2018; 78(2): 249 – 61. Dandurand M, Petit T, Martel P, Guillot B. Management of basal cell carcinoma in adults clinical practice guidelines. Eur J Dermatol 2006; 16: 394 –401. Silverman MK , Kopf AW, Bart RS et al. Recurrence rates of treated basal cell carcinomas. Part 3: Surgical excision. J Dermatol Surg Oncol 1992; 18: 471 – 6. Lo JS, Snow SN, Reizner GT et al. Metastatic basal cell carcinoma: report of twelve cases with a review of the literature. J Am Acad Dermatol 1991; 25: 715– 9. Cho M, Lee J, James CL et al. Scalp basal cell carcinoma: review of 2,202 cases. Dermatol Surg 2016; 42( 7): 834 –41. Suppa M, Micantonio T, Di Stefani A et al. Dermoscopic variability of basal cell carcinoma according to clinical type and anatomic location. J Eur Acad Dermatol Venereol 2015; 29: 1732 –41. Wolner Z, Bajaj S, Flores E et al. Variation in dermoscopic features of basal cell carcinoma as a function of anatomical location and pigmentation status. Br J Dermatol 2018; 178: e136 –7.


747

CME Article

20 21

22 23

24 25 26

27

28

29

30

31 32

33 34 35 36 37 38 39

40 41 42 43

748

Zalaudek I, Schmid K , Niederkorn A et al. Proposal for a clinical-dermoscopic classification of scalp naevi. Br J Dermatol 2014; 170: 1065–72. Costa S, Byrne M, Pissaloux D et al. Melanomas associated with blue nevi or mimicking cellular blue nevi: clinical, pathologic, and molecular study of 11 cases displaying a high frequency of GNA11 mutations, BAP1 expression loss, and a predilection for the scalp. Am J Surg Pathol 2016; 40 ( 3): 368 –77. Smith VA , Lentsch EJ. Sentinel node biopsy in head and neck desmoplastic melanoma: An analysis of 244 cases. The Laryngoscope 2012; 122: 116 –20. Cappello ZJ, Augenstein AC, Potts KL et al. Sentinel lymph node status is the most important prognostic factor in patients with melanoma of the scalp. The Laryngoscope 2013; 123: 1411 – 5. Rigual NR , Cheney RT, Iwenofu OH et al. Idiosyncrasies of scalp melanoma. The Laryngoscope 2007; 117: 1354 – 8. Saltman BE, Ganly I, Patel SG et al. Prognostic implication of sentinel lymph node biopsy in cutaneous head and neck melanoma. Head Neck 2010;32(12): 1686 – 92. Milton GW, Shaw HM, McCarthy WH et al. Prophylactic lymph node dissection in clinical stage I cutaneous malignant melanoma: results of surgical treatment in 1,319 patients. Br J Surg 1982; 69: 108 –11. Leong SP, Accortt NA , Essner R et al. Impact of sentinel node status and other risk factors on the clinical outcome of head and neck melanoma patients. Arch Otolaryngol Head Neck Surg 2006; 132: 370 –3. Gillgren P, Mansson-Brahme E, Frisell J et al. A prospective population-based study of cutaneous malignant melanoma of the head and neck. Laryngoscope 2000; 110: 1498 – 504 . Huismans AM, Haydu LE, Shannon KF et al. Primary melanoma location on the scalp is an important risk factor for brain metastasis: a study of 1,687 patients with cutaneous head and neck melanomas. Ann Surg Oncol 2014; 21(12): 3985– 91. Fadaki N, Li R , Parrett B et al. Is head and neck melanoma different from trunk and extremity melanomas with respect to sentinel lymph node status and clinical outcome? Ann Surg Oncol 2013; 20 (9): 3089 – 97. Tas F, Erturk K . Scalp melanoma is associated with high mitotic rate and is a poor prognostic factor for recurrence and outcome. Melanoma Res 2017; 27(4): 387– 90. Lachiewicz AM. Survival differences between patients with scalp or neck melanoma and those with melanoma of other sites in the surveillance, epidemiology, and end results (SEER) program. Arch Dermatol 2008;144(4): 515–21. Zelger B, Kazakov D, Zelger B. Klinik der Hautadnextumoren. Pathologe 2014; 35: 487. Burgdorf WHC. Cancer-associated genodermatoses. In: Burg G (ed.). Atlas of cancer of the skin. Churchill Livingstone Elsevier, London, 2000; 198 –208. Kazakov DV, McKee PH, Michal M, Kacerovska D. Cutaneous Adnexal Tumors, 1st ed, Lippincott Williams & Wilkins Health, Philadelphia, 2012. Barnes M, Hestley A , Murray DR et al. The risk of lymph node involvement in malignant cutaneous adnexal tumors. Am Surg 2014; 80 ( 3): 270 –4 . lsaad KO, Obaidat NA , Ghazarian D. Skin adnexal neoplasms – part 1: An approach to tumours of the pilosebaceous unit . J Clin Pathol 2007; 60 (2): 129 –44 . Martinez SR , Barr KL, Canter RJ. Rare tumors through the looking glass: an examination of malignant cutaneous adnexal tumors. Arch Dermatol 2011; 147(9): 1058 – 62. Kurokawa I, Senba Y, Nishimura K et al. Cytokeratin expression in trichilemmal carcinoma suggests differentiation towards follicular infundibulum. In Vivo 2006; 20: 583 – 5. Müller CS, Körner R , Takacs FZ et al. Metastatic breast carcinoma mimicking a sebaceous gland neoplasm: a case report . J Med Case Rep 2011; 5: 428. Swanson MS, Sinha UK . Diagnosis and management of Merkel cell carcinoma of the head and neck: current trends and controversies. Cancers 2014; 6( 3): 1256 – 66. Tilling T, Wladykowski E, Failla AV et al. Immunohistochemical analyses point to epidermal origin of human Merkel cells. Histochem Cell Biol 2013; 141: 407–21. Sauer CM , Chteinberg E , Rennspiess D et al. Merkel cell carcinoma: cutaneous manifestation of a highly malignant pre-/pro-B cell neoplasia? Hautarzt 2017; 68: 204 – 10.


CME Article

44

45 46

47 48 49 50 51 52 53 54 55 56 57

58 59 60

61 62

63 64 65 66 67 68 69

Smith VA , Camp ER , Lentsch EJ. Merkel cell carcinoma: Identification of prognostic factors unique to tumors located in the head and neck based on analysis of seer data. Laryngoscope 2012; 122: 1283 – 90. Allen PJ, Bowne WB, Jaques DP et al. Merkel cell carcinoma: Prognosis and treatment of patients from a single institution. J Clin Oncol 2005; 23: 2300 – 9. Becker JC, Stang A , Hausen A et al. Epidemiology, biology and therapy of Merkel cell carcinoma: conclusions from the EU project IMMOMEC. Cancer Immunol Immunother 2018; 67: 341. Willemze R , Jaffe ES, Burg G. WHO-EORTC classification for cutaneous lymphomas. Blood 2005; 105: 3768. Tan LA , Kasliwal MK , Arvanitis LD, Byrne RW. Enlarging scalp mass. J Neurooncol 2015; 122: 419 –20. Chan DY, Chan DT, Poon WS, Wong GK . Primary cranial vault lymphoma. Br J Neurosurg 2016; 13: 1 –2. Miteva M, El Shabrawi-Caelen L, Fink-Puches R et al. Alopecia universalis associated with cutaneous T cell lymphoma. Dermatology 2014; 229 (2): 65– 9. Imran MB, Othman S, Shahid A . Unusual presentation of mycosis fungoides as a lump in the scalp. Singapore Med J 2011; 52(11): 226 – 8. Somasekharan Nair KK , Zabell AS, Vo K-L, Shaikh MA . Pneumothorax: A classical presentation of metastatic scalp angiosarcoma. Ann Thorac Surg 2012; 94( 3): 77– 8. Luke JJ, Keohan ML. Advances in the systemic treatment of cutaneous sarcomas. Semin Oncol 2012; 39 (2): 173 – 83. Mendenhall W, Mendenhall CM, Werning JW et al. Cutaneous angiosarcoma. Am J Clin Oncol 2006; 29: 524 – 8. Leung LK . Differential diagnosis of soft scalp lumps. BMJ Case Rep 2011; 2011. pii: bcr0720114492.2011. Schulman JM, Pauli ML, Neuhaus IM et al. The distribution of cutaneous metastases correlates with local immunologic milieu. J Am Acad Dermatol 2016; 74( 3): 470 – 6. Lookingbill DP, Spangler N, Helm KF. Cutaneous metastases in patients with metastatic carcinoma: a retrospective study of 4020 patients. J Am Acad Dermatol 1993; 29: 228 –36. Hussein MR. Skin metastasis: a pathologist’s perspective. J Cutan Pathol 2010; 37(9): e1 –20. Bergman KS, Harris BH. Scalp and neck masses. Pediatr Clin North Am 1993; 40 (6): 1151 – 60. Depeyre A , Barthelemy I, Dechelotte P, Dang NP. A case of basaloid degeneration of nevus sebaceous during childhood: should nevus sebaceous be excised or followed up? Facial Plast Surg 2016; 32( 5): 576 –7. Cribier B, Scrivener Y, Grosshans E. Tumors arising in nevus sebaceus: A study of 596 cases. J Am Acad Dermatol 2000; 42: 263 – 8. Kallini JR , Hamed N, Khachemoune A . Squamous cell carcinoma of the skin: epidemiology, classification, management, and novel trends. Int J Dermatol 2015; 54(2): 130 –40. Li WQ , Cho E, Han J et al. Male pattern baldness and risk of incident skin cancer in a cohort of men. Int J Cancer 2016; 139 (12): 2671 – 8. Shore RE, Moseson M, Xue X et al. Skin cancer after X-ray treatment for scalp ringworm. Radiat Res 2002; 157: 410 – 8. Sheil AG, Disney APS, Mathew TG et al. Malignancy following renal transplantation. Transplant Proc 1992; 24: 1946 –7. Benjamin CL, Ananthaswamy HN. p53 and the pathogenesis of skin cancer. Toxicol Appl Pharmacol 2007; 224( 3): 241 – 8. Pillemerm BBL, Pugliano-Mauro MA , Ferris LK , Patton TJ. Three cases of scalp melanomas discovered by hairdressers. J Clin Aesthet Dermatol 2013; 6(8): 32 –4 . Bekiesinska-Figatowska M, Szczygielski O, Boczar M et al. Neurocutaneous melanosis in children with giant congenital melanocytic nevi. Clinical Imaging 2014; 38: 79 – 84 . Waelchli R , Aylett SE, Atherton D et al. Classification of neurological abnormalities in children with congenital melanocytic naevus syndrome identifies MRI as the best predictor of clinical outcome. Br J Dermatol 2015; 173( 3): 739 – 50.


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82 83 84 85 86 87

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91

750

Lewis JS. Spindle cell lesions – neoplastic or non-neoplastic?: spindle cell carcinoma and other atypical spindle cell lesions of the head and neck. Head and Neck Pathology 2008; 2(2): 103 –10. Leiter U, Eigentler TK , Häfner HM et al. Sentinel lymph node dissection in head and neck melanoma has prognostic impact on disease-free and overall survival. Ann Surg Oncol 2015; 22(12): 4073 – 80. Navarrete-Dechent C, Veness MJ, Droppelmann N et al. High-risk cutaneous squamous cell carcinoma and the emerging role of sentinel lymph node biopsy: a literature review. J Am Acad Dermatol 2015; 73: 127–37. Wong SL, Faries MB, Kennedy EB et al. Sentinel lymph node biopsy and management of regional lymph nodes in melanoma: American Society of Clinical Oncology and Society of Surgical Oncology Clinical Practice Guideline Update. Ann Surg Oncol 2018; 25: 356. Eder J, Prillinger K , Korn A et al. Prevalence of actinic keratosis among dermatology outpatients in Austria. Br J Dermatol 2014; 171: 1415–21. Werner RN, Stockfleth E, Connolly SM et al. Evidence and consensus Based (S3) Guidelines for the Treatment of Actinic Keratosis International League of Dermatological Societies (ILDS) in Cooperation with the European Dermatology Forum (EDF), 2014. Available from: http: //www.euroderm.org/edf/index.php/edf-guidelines/category/5guidelines-miscellaneous [Last accessed May 3, 2018]. August PJ. Cryotherapy of nonmelanoma skin cancer. Clinics in Dermatol 1995; 13(6): 589 – 92. Arenberger P, Arenbergerova M. New and current preventive treatment options in actinic keratosis. J Eur Acad Dermatol Venereol 2017; 31 (Suppl. 5): 13 –7. Nakayama M, Tabuchi K , Nakamura Y, Hara A . Basal cell carcinoma of the head and neck. J Skin Cancer 2011; 496910. Stratigos A , Garbe C, Lebbe C et al. Diagnosis and treatment of invasive squamous cell carcinoma of the skin: European consensus-based interdisciplinary guideline. Eur J Cancer 2015; 51(14): 1989 –2007. Kinsler VA , Bulstrode N et al. The role of surgery in the management of congenital melanocytic naevi in children: a perspective from Great Ormond Street Hospital. J Plast Reconstr Aesthet Surg 2009; 62( 5): 595– 601. Wramp ME, Langenbruch A , Augustin M et al. Clinical course, treatment modalities, and quality of life in patients with congenital melanocytic nevi – data from the German CMN registry. J Dtsch Dermatol Ges 2017; 15: 159 – 67. Krengel S, Hauschild A , Schäfer T. Melanoma risk in congenital melanocytic naevi: a systematic review. Br J Dermatol 2006; 155: 1 – 8. Jang MS, Baek JW, Park JB et al. Large superficial basal cell carcinoma arising in the scalp. Ann Dermatol 2011; 23 (1): 96 – 9. Scheffka D, Zutt M. Critical situations in the wound closure of the scalp – How they might be avoided. Akt Dermatol 2015; 41: 294 – 9. Miklavcˇicˇ D, Mali B, Kos B et al. Electrochemotherapy: from the drawing board into medical practice. BioMedical Engineering OnLine 2014; 13: 29. Calvet CY, Mir LM. The promising alliance of anti-cancer electrochemotherapy with immunotherapy. Cancer Metastasis Rev 2016; 35: 165–77. Andtbacka RH, Kaufman HL, Collichio F et al. Talimogene laherparepvec improves durable response rate in patients with advanced melanoma. J Clin Oncol 2015;33(25): 2780 – 8. Shin JY, Roh SG, Lee NH, Yang KM. Predisposing factors for poor prognosis of angiosarcoma of the scalp and face: Systematic review and meta-analysis. Head Neck 2017; 39 (2): 380 – 6. Cölog ˇlu H, Ozkan B, Sener M et al. The management of non-melanocytic skin malignancies of the scalp and calvarium. Indian J Plast Surg 2014; 47(1): 36 –42. Veness MJ, Porceddu S, Palme CE et al. Cutaneous head and neck squamous cell carcinoma metastatic to cervical lymph nodes (nonparotid): a better outcome with surgery and adjuvant radiotherapy. Laryngoscope 2003; 113(10): 1827–33. Kruse-Lösler B, Presser D, Meyer U. Reconstruction of large defects on the scalp and forehead as an interdisciplinary challenge: Experience in the management of 39 cases. EJSO 2006;32: 1006 –14 .


CME Article

92

93 94

95 96 97

Kazakov D. Adnextumoren mit Talgdrüsen-und Haarfollikeldifferenzierung. In: Cerroni L et al. (Hrsg). Histopathologie der Haut . Springer, Berlin, Heidelberg, New York, 670 –1. Castori M, Morrone A , Kanitakis J, Grammatico P. Genetic skin diseases predisposing to basal cell carcinoma. Eur J Dermatol 2012; 22( 3): 299 –309. Morón FE, Morriss MC, Jones JJ, Hunter JV. Lumps and bumps on the head in children: Use of CT and MR imaging in solving the clinical diagnostic dilemma. RadioGraphics 2004; 24,6: 1655–74 . Fahradyan A , Howell AC, Wolfswinkel EM et al. Updates on the management of nonmelanoma skin cancer (NMSC). Healthcare 2017; 5(4): 82. Liu B, Song Y, Liu D. Recent development in clinical applications of PD-1 and PD-L1 antibodies for cancer immunotherapy. J Hematol Oncol 2017; 10: 174 . Chan IS, Bhatia S, Kaufman HL, Lipson EJ. Immunotherapy for Merkel cell carcinoma: a turning point in patient care. J Immunother Cancer 2018; 6: 23.


751

CME Article

Fragen zur Zertifizierung durch die DDA 1.

Nichmelanozytäre Hauttumoren

3.

6.

Eine erhöhte UV-Exposition spielt

stellen die größte Gruppe der malignen

für die Kopfhaut besitzt auch bei in-

in der Pathogenese vieler (Kopfhaut-)

Kopfhauttumoren dar. Welche Aussage

itial durchgeführter, weiter Exzision

Tumoren eine entscheidende Rolle. Wel-

ist für diese Subgruppe zutreffend? a) Plattenepithelkarzinome werden an der Kopfhaut erfreulicherweise meist schon in einem frühen Stadium erstdiagnostiziert. b) Basalzellkarzinome rezidivieren an der Kopfhaut nur in Ausnahmefällen. c) Melanozytäre Muster im Auflicht sind für das Plattenepithelkarzinom der Kopfhaut typisch. d) Kryotherapie kann als verhältnismäßig zeiteffiziente und kostengünstige Modalität zur Destruktion von invasiven Plattenepithelkarzinomen sowie nodulären Basalzellkarzinomen herangezogen werden. e) Risikofaktoren für die Entstehung nichtmelanozytärer Kopfhauttumoren inkludieren UV-Exposition, stattgehabte Radiotherapie, chronische Wunden und Immunsuppression.

(2–3 cm Sicherheitsabstand) eine star-

cher Kopfhauttumor ist (nach aktuellem

ke Tendenz zum Lokalrezidiv und kann

Erkenntnisstand) am wenigsten mit

zudem zahlreiche (banale) Hautverän-

diesem externen Risikofaktor assoziiert? a) Basaliom b) Plattenepithelkarzinom c) Melanom d) kutanes Lymphom e) Merkelzellkarzinom

derungen imitieren? a) Dermatofibrosarcoma protuberans b) Lentigo-maligna-Melanom c) Angiosarkom d) multifokales Basaliom e) Merkelzellsarkom

7. 4.

Kopfhauttumoren bei Kindern

Sämtliche genetische Syndrome

gleich zu anderen Lokalisationen eine

Bei welchem Syndrom ist diese Assozi-

schlechtere Prognose. Bei welchem der

ation nicht typisch? a) Brooke-Spiegler-Syndrom b) familiäre Zylindromatose c) SCALP-Syndrom d) Netherton-Syndrom e) Muir-Torre-Syndrom

folgenden Tumoren ist eine frühzeitige

Eine chirurgische Exzision von

kleinen und mittelgroßen kongenita-

sind zwar selten und überwiegend

len Nävi wird im Unterschied zu vor

benigne, die Liste an Differenzialdia-

einigen Jahren mittlerweile nur mehr

gnosen ist jedoch groß. Bei welchem

sehr restriktiv vorgenommen. Was ist

klinischen Kriterium sollte man früh-

der Grund für die Änderung des Vor-

zeitig eine radiologische Abklärung

gehens? a) Ein chirurgischer Eingriff erhöht das Melanomrisiko. b) Das maligne Transformationsrisiko wurde fälschlicherweise zu hoch angesehen. c) Das kosmetische Ergebnis ist postoperativ in den meisten Fällen wenig zufriedenstellend. d) Nach einer Exzision kommt es in einem Großteil der Fälle zu einem Rezidiv. e) Die meisten kongenitalen Nävi werden heutzutage mittels Laser therapiert.

vornehmen? a) Lokalisation okzipital lateral b) fehlende Verschieblichkeit beziehungsweise Lokalisation in der Mittellinie c) langsames Wachstum d) unbehaarter Tumor e) Regressionszeichen von vaskulären Läsionen

Viele maligne Tumoren, die an

der Kopfhaut auftreten, haben im Ver-

sind mit Kopfhauttumoren assoziiert.

5. 2.

752

Welcher Tumor mit Prädilektion


Diagnose und Therapieeinleitung entscheidend, um potenzielle Komplikationen durch Infiltration/Invasion tieferer Strukturen (z. B. Schädelknochen) zu vermeiden? a) mikrozystisches Adnexkarzinom b) superfizielles Basaliom c) Lentigo maligna Melanom d) Nävus sebaceus mit Trichoblastom e) proliferierende tricholemmale Zyste

8.

Kopfhauttumoren stellen nicht

zuletzt aufgrund ihrer Heterogenität eine diagnostische Herausforderung. Welche der folgenden Aussagen trifft nicht über die diagnostischen Maßnahmen zu? a) Schildwächter-LymphknotenBiopsien werden aufgrund der hohen falschpositiven Rate bei Kopfhautmelanomen kritisch bewertet. b) Diagnoseverzögerungen sind häufig, da die Früherkennung von Kopfhauttumoren durch (dichte) Behaarung und (in Selbstinspektion) schwer einsehbaren Bereichen an der Kopfhaut erschwert wird.

CME Article

c)

d)

e)

9.

Shavingbiopsien im Rahmen der Abklärung von Tumoren sollten vor allem aufgrund der mikromorphologischen Besonderheiten an der Kopfhaut vermieden werden. Nichtinvasive diagnostische Methoden (z. B. Dermatoskopie) können ergänzend zur differenzialdiagnostischen Abklärung herangezogen werden. Bei großen kongenitalen Nävi (> 20 cm) und solchen, die mit Satellitennävi einhergehen, wird zur weiteren Abklärung eine kraniale MR-Untersuchung empfohlen

Welche der folgenden Aussagen

über Kopfhauttumoren ist richtig? a) Kutane Metastasen führen die Rangliste der häufigsten malignen Kopfhauttumoren an. b) Lipome und Fibrome bilden zusammen die größte Gruppe der benignen Kopfhauttumoren. c) Die hohe Anzahl an apokrinen Schweißdrüsen prädisponiert die Kopfhaut als Prädilektionsort für Atherome.

d) e)

1–2 % aller Kopfhauttumoren sind maligne. Der Häufigkeitsgipfel für die Entstehung maligner Kopfhauttumoren liegt zwischen dem 40. und 60. Lebensjahr.

10. Welche Aussage zu melanozytären Kopfhautumoren ist richtig? a) Kopfhautnävi zeigen im Vergleich zur restlichen Körperhaut histopathologisch selten dysplastische Merkmale. b) Dermatoskopisch sind blau-graue ovoide Nester typisch. c) GNA11-mutierte blaue Nävi zeigen eine Prädilektion für die Kopfhaut und haben ein erhöhtes Entartungsrisiko. d) Die Rate falsch positiver regionaler Schildwächterlymphknoten ist beim Kopfhautmelanom höher. e) Kopfhautmelanome verantworten 45 % der Todesfälle durch schwarzen Hautkrebs.


Liebe Leserinnen und Leser,

der Einsendeschluss an die DDA für diese Ausgabe ist der 31. Juli 2018. Die richtige Lösung zum Thema „Lipomatosen“ in Heft 3 (März 2018) ist: (1e, 2d, 3a, 4b, 5b, 6b, 7e, 8a, 9c, 10a). Bitte verwenden Sie für Ihre Einsendung das aktuelle Formblatt auf der folgenden Seite oder aber geben Sie Ihre Lösung online unter http://jddg. akademie-dda.de ein.

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