JEADV
DOI: 10.1111/jdv.13092
ORIGINAL ARTICLE
Clinical, histopathological, dermatoscopic and digital microscopic features of dermatofibroma: a retrospective analysis of 200 lesions ruer S E. S ß enel,1,* Y. Yuyucu Karabulut,2 S. Dog ß enel3 Faculty of Medicine, Department of Dermatology, Hitit University, C ß orum, Turkey Faculty of Medicine, Department of Pathology, Mersin University, Mersin, Turkey 3 Faculty of Economics, Department of Public Administration, Anadolu University, Eskisßehir, Turkey *Correspondence: E. S ß enel. E-mail: [email protected] 1 2
Abstract Background Dermatology literature lacks a study investigating both histopathological and dermatoscopic features of dermatofibroma. Objective To analyse histopathological, dermatoscopic and digital microscopic features of dermatofibromas. Methods Two hundred dermatofibromas and 190 patients were included and retrospectively evaluated. Nine histopathological and ten dermatoscopic patterns were used to classify the lesions. We identified four different types of dermatofibroma in digital microscopy. Results The mean age of the patients was 42.18 13.72 years. Dermatofibroma was more common in females (67%) and the male to female ratio was 1 : 1.97. The most common location was leg (41%). The most frequent histopathological variant was fibrocollagenous type (49%). Grenz zone was the most common histopathological finding (89%). The most frequent digital microscopic type was type 1 (63%). Conclusions We found that palisading variant displayed only pattern 6 in dermatoscopy and cellular variant showed type 3 significantly in digital microscopy. Received: 11 September 2014; Accepted: 12 February 2015
Conflict of interest None.
Funding source None.
Dermatofibromas also known as benign fibrous histiocytomas are common benign mesenchymal fibrosing cutaneous tumours clinically characterized by the ‘dimple sign’ when laterally squeezed.1 They are often found on the legs. The aetiology still remains unclear.2,3 Although histopathology is the gold standard for a definite diagnosis, dermatoscopy has been proven to be useful tool to distinguish dermatofibroma from other pigmented skin lesions.4 In a recent study by Zaballo et al.5, 10 different dermatoscopic patterns were reported. Although there are several studies examining histopathology or dermatoscopy of dermatofibromas separately1,5–12 the literature lacks a study investigating both in the same patient group. In the present study, we aimed to analyse histopathological, dermatoscopic and digital microscopic features of dermatofibromas. To the best of our knowledge, this is first report discussing digital microscopic patterns of dermatofibroma.
JEADV 2015, 29, 1958–1966
Methods Two hundred dermatofibromas of 190 consecutive patients from the patient archive of our clinic between August 2013 and June 2014 were retrospectively evaluated and included in the present study. Our hospital is a tertiary health centre in C ß orum which is a province in the Black Sea Region of Turkey. Demographic data, clinical findings and clinical, histopathological, dermatoscopic and digital microscopic images were collected from medical records. Histopathological diagnosis was reviewed according to histopathological features and variants of dermatofibroma reported in the recent studies.3,6,10 We followed the classification consisting of 10 patterns identified by Zaballos et al.5 to group dermatoscopic findings of the cases in our study. We evaluated digital images obtained by a dermatoscope (Dermlite DL-1, 3Gen Inc, San Juan Capistrano, CA, USA) and a handheld digital microscope (Model 44301, Clam Shell, Celestron, LLC,
© 2015 European Academy of Dermatology and Venereology
Features of dermatofibroma
1959
Torrance, CA, USA). Dermatoscopic images were 3264 9 2448 pixels, JPEG formatted with 10-fold magnification and digital microscopic images were 1280 9 1024 pixels, JPEG formatted with 30-fold magnification. Statistical analysis was performed using chi-squaredand Fisher’s exact tests.
Results Demographic and clinical findings
The mean age of the patients was 42.18 13.72 years ranging from 14 to 81 years. Dermatofibromas were more common in females (n = 126, 66.3%) than males (n = 64, 33.7%) and the male to female ratio was 1 : 1.97. Most patients had a solitary lesion (n = 181, 95.3%). Eight patients had two and only one patient had three lesions. The fifth decade was the peak for the women (38.9%) although the highest frequency was in the fourth decade for men (25%) (Fig. 1). Twelve lesions (6%) occurred at the sites of trauma. Most lesions were asymptomatic (82.5%). Pruritus was the most common symptom (12.5%) followed by pain (5.5%). The most common location of dermatofibromas was leg (41%) followed by arm (24%), back (11%) and chest (7.5%) (Fig. 2). Histopathological findings
Histopathological examination revealed nine different dermatofibroma variants. The most frequent variant of dermatofibroma was fibrocollagenous type (n = 98, 49%) followed by sclerotic (n = 38, 19%), histiocytic (n = 26, 13%) and cellular (n = 16, 8%) (Figs. 3–10). The depth of 59.5% of the samples was dermis. Only 6.5% of the lesions reached deep subcutaneous region. Grenz zone was the most common histopathological finding and seen in 89% of the cases. Hyperkeratosis was the most frequent epidermal change in all variants and found in almost all of fibrocollagenous type tumours (94%). Lymphoid nodules in the dermo-subcutaneous junction were observed in 14 cases and most of them were cellular variant (Figs 3–10). Mucin deposition
Figure 2 Distribution of dermatofibroma localizations.
was noted only in histiocytic and fibrocollagenous variants (23.1% and 8.5% respectively) and it was statistically higher in histiocytic variant (P < 0.001) (Table 1). The most frequent histopathological variant of the tumours located on legs was fibrocollagenous (47.5%) followed by sclerotic (28%) and histiocytic (8.5%). Fibrocollagenous variant was also dominant for the localizations of abdomen (100%), arm (68.7%), buttock (50%) and chest (46.7%) although it was not found on the samples from palmoplantar region (Table 2). Dermatoscopic findings
Our cases included eight of ten dermatoscopic patterns that Zaballos et al.5 identified. Half of the cases (50.5%) were in type 2 pattern with peripheral pigment network and central white scar-like patch (Fig. 11). Pattern 2 was the major dermatoscopic appearance (50%) for dermatofibromas located on legs followed by pattern 1 (28%) and pattern 3 (7.3%). It was also the dominant pattern for other certain localizations such as chest (80%), back (50%) and arm (70.8%). Dermatofibromas on face and hands displayed most commonly pattern 1 with total
Figure 1 Age and gender distribution of the cases.
JEADV 2015, 29, 1958–1966
© 2015 European Academy of Dermatology and Venereology
S ß enel et al.
1960
Figure 3 Fibrocollagenous type of dermatofibroma with orthokeratosis, irregular acanthosis and basal pigmentation and predominance of collagen and fibroblasts in a wavy arrangement (H&E, 9100).
Figure 5 Cellular type with high cellularity and short fascicular growth pattern (H&E, 9200).
Figure 6 Aneurysmal type characterized by blood-filled vascular spaces (H&E, 9400). Figure 4 Histiocytic type showing sheets of histiocytes (H&E, 9100).
delicate network located throughout the lesion (40% and 70%, respectively) (Table 3) (Fig. 12). Regarding evaluation of dermatoscopic patterns according to histopathological variants, pattern 2 was the most frequent in fibrocollagenous (47.9%), histiocytic (46.1%), angiomatous (75%) and sclerotic (68.4%) types. Patterns 1 and 2 were found equally in keloidal and cellular variants (40% and 37.5% respectively) (Table 4). In dermatoscopic examination pigment network was the most common feature (n = 133, 66.5%) followed by white scar-like
JEADV 2015, 29, 1958–1966
patch (109, 54.5), brown dots and globules (69, 34.5%) and vascular structures (n = 63, 31.5%). The lowest ratio for pigment network was detected in the sclerotic histopathological variant (0%). Palisading variant lesions showed only dermatoscopic pattern 6 with homogenous pigmentation throughout the lesion (100%). Nearly all tumours with aneurismal and angiomatous variants had vascular features in dermatoscopy (100% and 87.5%, respectively) (Table 4). Digital microscopic findings
Digital microscopy is a non-invasive technique providing 30–100-fold magnification of melanocytic and non-melanocytic
© 2015 European Academy of Dermatology and Venereology
Features of dermatofibroma
1961
Figure 7 Sclerotic type showing hyalinized eosinophilic collagen bundles (H&E, 9200).
Figure 9 Palisading type with verocay-like bodies (H&E, 9100).
Figure 8 Monster type with large, hyperchromatic, bizarre nuclei (H&E, 9400).
Figure 10 Keloidal type with broad, thick and irregularly oriented collagen bundles (H&E, 9100).
skin lesions. A digital microscope is more affordable tool than a dermatoscope. We evaluated a total of 200 dermatofibroma images obtained by a 30-fold magnifying digital handheld microscope. We identified four different types of dermatofibroma in digital microscopy with following features: Type 1: Central scar-like appearance and peripheral pigmentation (Fig. 13) Type 2: Homogenous brown pigmentation (Fig. 14) Type 3: Homogenous-pigmented nodule (Fig. 15) Type 4: Heterogeneous pigmentation with normal-appearing areas (Fig. 16) The most frequent digital microscopic type was type 1 (63%) followed by type 3, 2 and 4 (16%, 13% and 8% respectively).
Type 1 was the prominent pattern in all localizations except for abdomen (Table 5). Type 1 was also most common for all histopathological variants but cellular variant. Digital microscopic examination disclosed type 3 appearance in 68.8% of dermatofibromas with cellular variant (Table 6).
JEADV 2015, 29, 1958–1966
Discussion Although dermatofibromas clinically exhibit the ‘dimple sign’ when laterally squeezed it sometimes may be difficult to distinguish them from certain skin neoplasms such as dermatofibrosarcoma protuberans (DFSP), leiomyosarcoma and amelanotic melanoma. Amelanotic melanoma has more pleomorphism and epidermal involvement with S100 positivity. Dermatofibroma
© 2015 European Academy of Dermatology and Venereology
JEADV 2015, 29, 1958–1966
8 (50.0)
Palisading (2, 1%)
Cellular (16, 8%) 60 (30.0)
6 (37.5)
2 (100)
6 (15.8)
4 (40.0)
0 (0)
2 (25.0)
0 (0)
8 (30.8)
32 (34.0)
18 (9.0)
2 (12.5)
0 (0)
2 (5.3)
0 (0)
2 (100)
4 (50.0)
2 (50.0)
0 (0)
6 (6.4)
2 (40)
94 (47)
Total (100%)
7 (50)
Buttock (7%)
Face (2.5%)
4 (18.2)
Back (11%)
33 (68.7)
2 (100)
Arm (24%)
7 (46.7)
Abdomen (1%)
–
Hand (5%)
Chest (7.5%)
39 (47.5)
–
Leg (41%)
Fibrocollagenous
3 (60)
5 (10.4)
3 (13.6)
5 (33.3)
3 (30)
7 (8.5)
26 (13)
–
–
–
Histiocytic
Histopathological variant
Foot (1%)
Localization (%)
2 (2.4)
8 (4)
–
– 4 (2)
– 1 (2.1)
–
5 (22.7)
– –
–
–
– –
–
2 (20)
–
– 2 (100)
Angiomatous
172 (86.0)
14 (87.5)
2 (100)
30 (78.9)
8 (80.0)
2 (100)
6 (75.0)
2 (50.0)
20 (76.9)
88 (93.6)
Aneurysmal
Table 2 Histopathological variants according to localizations
122 (61.0)
0 (0)
Sclerotic (38, 19%)
Total (200, 100%)
6 (60.0)
30 (78.9)
Keloidal (10, 5%)
2 (25.0)
0 (0)
2 (50.0)
Aneurysmal (4, 2%)
Monster (2, 1%)
18 (69.2)
Histiocytic (26, 13%)
Angiomatous (8, 4%)
56 (59.6)
Hyperkeratosis (%)
Deep subcutaneous (%)
Dermis (%)
Superficial subcutaneous (%)
Epidermal change
Invasion depth
Fibrocollagenous (94, 47%)
Type (n, %)
Table 1 Histopathological features of dermatofibroma variants
2 (1)
–
–
–
–
–
–
–
–
2 (2.4)
Monster
162 (81.0)
16 (100)
2 (100)
32 (84.2)
8 (80.0)
2 (100)
6 (75.0)
2 (50.0)
20 (76.9)
74 (78.7)
Acanthosis (%)
3 (6.2)
3 (30)
4 (4.8)
10 (5)
–
–
–
–
–
–
Keloidal
114 (57)
8 (50)
2 (100)
20 (52.6)
4 (40)
2 (100)
6 (75.0)
2 (50.0)
10 (38.5)
60 (63.8)
2 (4.2)
3 (21.4)
5 (22.7)
3 (20)
38 (19)
–
–
2 (20)
23 (28) –
2 (1)
–
–
1 (7.1)
1 (4.5)
–
–
–
–
–
Palisading
178 (89.0)
14 (87.5)
2 (100)
38 (100)
10 (100)
2 (100)
8 (100)
2 (50.0)
20 (76.9)
82 (87.2)
Sclerotic
Basal Pigmentation (%)
Grenz zone (%)
4 (8.3)
3 (21.4)
4 (18.2)
5 (6.1)
16 (8)
–
–
–
–
–
Cellular
14 (7.0)
6 (37.5)
2 (100)
0 (0)
0 (0)
0 (0)
0 (0)
2 (50.0)
0 (0)
4 (4.3)
Lymphoid nodule (%)
200
5
48
14
22
2
15
10
2
82
Total
14 (7.0)
0 (0)
0 (0)
0 (0)
0 (0)
0 (0)
0 (0)
0 (0)
6 (23.1)
8 (8.5)
Mucin (%)
1962
S ß enel et al.
© 2015 European Academy of Dermatology and Venereology
Features of dermatofibroma
1963
Figure 11 Pattern 2, the most common dermatoscopic pattern of dermatofibromas with peripheral pigment network and central scar-like white patch (dermatoscopy, 910).
Figure 12 Pattern 1, dermatoscopic pattern of dermatofibroma with total delicate network located throughout the lesion (dermatoscopy, 910).
may be confused with leiomyosarcoma and DFSP even in histopathological examination13. Leiomyosarcoma has spindleshaped nuclei, a more uniform fascicular pattern and a more obvious eosinophilic cytoplasm. DFSP lacks cytological polymorphism and epidermal changes and has a tighter fusiform pattern with CD34 positivity.13,14 There are a limited number of studies investigating histopathological and dermatoscopic features of dermatofibromas in the literature.1,5–7,10,11,13,15 As far as we aware, the present study is the first to evaluate both histopathological and dermatoscopic features of dermatofibromas. However, we implemented a preliminary assessment of digital microscopic features of dermatofibroma. Recent reports demonstrated that legs and arms were the most frequent localizations for dermatofibromas like in our study.5,6 The tumours of our patients were much deeper than those in a Korean study by Han et al. and the ratio of dermatofibromas located in deep subcutis was higher (9% vs. 3.3%). Dermatofibromas are composed of fibroblast-like cells, histiocytes and blood cells in histopathology. According to the predominance of three components, three terms ‘nodular subepidermal fibrosis’, histiocytoma’ and ‘sclerosing hemangioma’ were used in the past.16 Although a complete consensus has not been reached at present dermatofibromas are distinguished by their histopathological characteristics.10 Similar to our study Han et al.6 found that fibrocollagenous variant was the most common histopathological type of dermatofibroma (40.1%). Regarding epidermal changes, we found higher percentages of hyperkeratosis (86% vs. 67.2%) and acanthosis (81% vs. 74.4%), and a lower percentage of basal pigmentation (57% vs. 72.1%). Grenz zone was detected in a higher ratio in our study (89% vs. 71.3%) and lymphoid nodules in the dermo-subcutaneous junction and mucin deposition were noted lower (7% vs. 9.8% and 7% vs. 18.9% respectively). In a Portuguese study by Alves et al. lower hyperkeratosis (45%), acanthosis (77%) and basal pigmentation (64%) were detected. Moreover, they found lower percentages of presence of grenz zone (53%) and
Table 3 Dermatoscopic patterns according to localizations Localization (%)
Dermatoscopic pattern Pattern 1
Leg
23 (28.0)
Foot
–
Pattern 2 41 (50) –
Hand
7 (70)
Chest
2 (13.3)
Abdomen
1 (50)
Back
8 (36.4)
2 (20) 12 (80) –
6 (7.3)
Buttock
3 (21.4)
1 (7.1)
8 (16.7)
34 (70.8)
Face
2 (40)
Total
54 (27)
Pattern 4
Pattern 6
Pattern 7
Pattern 8
Pattern 10
Total
3 (3.7)
4 (4.9)
2 (2.4)
2 (2.4)
1(1.2)
–
–
2 (100)
–
–
–
–
–
–
–
–
1 (10)
10
82
15
2
–
1 (6.7)
–
–
–
–
–
–
–
–
1 (50)
–
2
2 (9.1)
–
1 (4.5)
–
–
22
–
9 (64.3)
–
1 (7.1)
–
14
6 (12.5)
–
–
–
–
–
48
11 (50)
Arm
JEADV 2015, 29, 1958–1966
Pattern 3
–
–
–
1 (20)
–
1 (20)
101 (50.5)
14 (7)
5 (2.5)
16 (8)
3 (1.5)
4 (2)
1 (20)
5
3 (1.5)
200
© 2015 European Academy of Dermatology and Venereology
S ß enel et al.
1964
Table 4 Dermatoscopic patterns according to histopathological variants Histopathology (%)
Dermatoscopic pattern Pattern 1
Fibrocollagenous (94, 47%)
Pattern 2
Pattern 8
Pattern 10
Total
8 (8.5)
3 (3.2)
4 (4.2)
2 (2.1)
4 (4.2)
2 (2.1)
94
12 (46.1)
4 (15.4)
–
3 (11.5)
–
–
1 (3.8)
26
2 (50)
2 (50) 2 (25)
–
–
Keloidal (10, 5%)
4 (40)
Sclerotic (38, 19%)
8 (21)
–
–
–
–
–
4
6 (75)
–
–
–
–
–
–
8
2 (100)
–
–
–
–
–
–
2
4 (40)
–
–
–
–
–
10 38
26 (68.4)
–
– 6 (37.5)
Total (200, 100%)
Pattern 7
45 (47.9)
Angiomatous (8, 4%)
Cellular (16, 8%)
Pattern 6
6 (23.1)
Aneurysmal (4, 2%)
Palisading (2, 1%)
Pattern 4
26 (27.6)
Histiocytic (26, 13%)
Monster (2, 1%)
Pattern 3
–
–
3 (7.9)
1 (2.6)
–
–
–
–
2 (100)
–
–
–
2 16
6 (37.5)
54 (27)
2 (12.5)
101 (50.5)
2 (20)
14 (7)
2 (12.5)
–
–
–
–
5 (2.5)
16 (8)
3 (1.5)
4 (2)
3 (1.5)
200
Table 5 Digital microscopic types according to localizations Localization
Digital dermatoscopic type Type 1
Leg Foot
52 (63.4) –
Hand
Type 3
10 (12.2)
16 (19.5)
4 (4.9)
–
–
2 (100)
8 (80)
Chest Abdomen
Type 2
12 (80) –
Back
9 (40.9)
Buttock
2 (20)
–
2 (13.3)
–
2 (100)
–
–
5 (35.7)
Type 4
–
2 (14.3)
7 (50)
7 (14.6)
2 (4.2)
Arm
36 (75)
Face
4 (80)
1 (20)
Total
126 (63)
26 (13)
82 2 10
1 (6.7)
15
6 (27.3)
22
– 7 (31.8)
Total
2
–
14 3 (6.2)
–
–
32 (16)
16 (8)
48 5 200
Table 6 Digital microscopic types according to histopathological variants Histopathology (%)
Digital dermatoscopic type Type 1
Type 2
Type 3
Type 4
Total
Fibrocollagenous (94, 47%)
59 (62.8)
15 (15.9)
11 (11.7)
9 (9.6)
94
Histiocytic (26, 13%)
14 (53.8)
7 (26.9)
3 (11.5)
2 (7.7)
26
Aneurysmal (4, 2%)
3 (75)
–
1 (25)
4
Angiomatous (8, 4%)
6 (75)
–
Monster (2, 1%)
2 (100)
–
Keloidal (10, 5%)
5 (50)
1 (10)
4 (40)
Sclerotic (38, 19%)
31 (81.6)
3 (7.9)
1 (2.6)
Palisading (2, 1%)
2 (100)
–
–
4 (25)
–
11 (68.8)
26 (13)
32 (16)
Cellular (16, 8%) Total (200, 100%)
126 (63)
JEADV 2015, 29, 1958–1966
– 2 (25) –
–
8
–
2
–
10 3 (7.9)
–
38 2
1 (6.2) 16 (8)
Figure 13 Type 1 with peripheral pigmentation and central scarlike appearance (digital microscopy, 930).
16 200
lymphoid nodules (3%). We observed that mucin deposition was statistically higher in histiocytic variant (P < 0.001) although Han et al. reported no difference among the variants. Four major dermatoscopic features of dermatofibroma have been identified in the literature. Arpaia et al. proposed three dermatoscopic types for dermatofibroma: (i) isolated pigment network (31%), (ii) peripheral pigment network associated with globules and dots or with scale crusts and sometimes also with central white patch (13%) and (iii) peripheral pigment network and a central white area (56%).5,15 Only 39 lesions were included in the study by Arpaia et al. and pigment network was found in all dermatofibromas. Therefore, no pattern without pigment network may have been proposed.15 We found a pigment network in 66.5% of the lesions (Table 7). We used dermatoscopic
© 2015 European Academy of Dermatology and Venereology
Features of dermatofibroma
Figure 14 Type 2 with homogenous brown pigmentation (digital microscopy, 930).
Figure 15 Type 3, homogenous-pigmented nodule (digital microscopy, 930).
patterns by Zaballo et al. as the most elaborated classification although we could find no lesion showing pattern 5 and 9. As we experienced in the present study it was hard to distinguish between pattern 8 with peripheral homogeneous pigmentation and central white scar-like patch and pattern 9 with peripheral homogeneous pigmentation and central white network. Digital microscopy was previously used in dermatology practice for the evaluation of morphology of molluscum contagiosum and seborrhoeic keratosis.17,18 Sßenel et al.19 recently
JEADV 2015, 29, 1958–1966
1965
Figure 16 Type 4 with homogenous pigmentation and normalappearing areas (digital microscopy, 930).
reported that digital microscopy increased significantly the diagnostic and therapeutic reliability of teledermatologic application in skin tumours. As far as we are aware, the present study is preliminary to perform an evaluation of the digital microscopic features of dermatofibroma. Dermatofibromas present different clinical appearances in dermatological examination. Fibrocollagenous variant in histopathology, pattern 2 in dermatoscopy and type 1 in digital microscopy were the most common diagnostic styles for dermatofibromas. Although none of the dermatoscopic or digital microscopic style reflected a specific histopathological variant, we found that palisading variant displayed only pattern 6 in dermatoscopy and cellular variant showed type 3 significantly in digital microscopy. Zaballos et al.5 reported that they were not able to elucidate the specificity of each dermatoscopic pattern for the diagnosis of dermatofibroma. As far as we experience, physicians may feel more comfortable with the major patterns, Type 2 dermatoscopic and Type 1 digital microscopic patterns, which reflect typical appearances in the diagnosis of dermatofibroma (Figs 11 and 13). Lesions with type 2 microscopic pattern may be confused with seborrhoeic keratosis (Fig. 14). Seborrhoeic keratosis can be easily distinguished in digital microscopy if the lesion presents milia-like cysts, pseudofollicular (comedo-like) openings, hyperkeratosis and cerebriform appearance. Type 3 microscopic pattern can be also seen in certain nodular lesions such as fibromas, Spitz nevi, dermal nevi or amelanotic melanomas. Histopathological evaluation should be performed for all the lesions with type 3 pattern although clinical examination leads the physician to the diagnosis of dermatofibroma (Fig. 15). Type 4 microscopic pattern
© 2015 European Academy of Dermatology and Venereology
S ß enel et al.
1966
Table 7 Frequency of dermatoscopic features reported in the literature Dermatoscopic feature
Agero et al. (%)12
Arpaia et al. (%)16
Ferrari et al. (%)11
Zaballos et al. (%)5
Pigment network
72
100
83
72
66.5
White scar-like patch
84
>56
92
57
54.5
Brown dots and globules
44
DOI: 10.1111/jdv.13092
ORIGINAL ARTICLE
Clinical, histopathological, dermatoscopic and digital microscopic features of dermatofibroma: a retrospective analysis of 200 lesions ruer S E. S ß enel,1,* Y. Yuyucu Karabulut,2 S. Dog ß enel3 Faculty of Medicine, Department of Dermatology, Hitit University, C ß orum, Turkey Faculty of Medicine, Department of Pathology, Mersin University, Mersin, Turkey 3 Faculty of Economics, Department of Public Administration, Anadolu University, Eskisßehir, Turkey *Correspondence: E. S ß enel. E-mail: [email protected] 1 2
Abstract Background Dermatology literature lacks a study investigating both histopathological and dermatoscopic features of dermatofibroma. Objective To analyse histopathological, dermatoscopic and digital microscopic features of dermatofibromas. Methods Two hundred dermatofibromas and 190 patients were included and retrospectively evaluated. Nine histopathological and ten dermatoscopic patterns were used to classify the lesions. We identified four different types of dermatofibroma in digital microscopy. Results The mean age of the patients was 42.18 13.72 years. Dermatofibroma was more common in females (67%) and the male to female ratio was 1 : 1.97. The most common location was leg (41%). The most frequent histopathological variant was fibrocollagenous type (49%). Grenz zone was the most common histopathological finding (89%). The most frequent digital microscopic type was type 1 (63%). Conclusions We found that palisading variant displayed only pattern 6 in dermatoscopy and cellular variant showed type 3 significantly in digital microscopy. Received: 11 September 2014; Accepted: 12 February 2015
Conflict of interest None.
Funding source None.
Dermatofibromas also known as benign fibrous histiocytomas are common benign mesenchymal fibrosing cutaneous tumours clinically characterized by the ‘dimple sign’ when laterally squeezed.1 They are often found on the legs. The aetiology still remains unclear.2,3 Although histopathology is the gold standard for a definite diagnosis, dermatoscopy has been proven to be useful tool to distinguish dermatofibroma from other pigmented skin lesions.4 In a recent study by Zaballo et al.5, 10 different dermatoscopic patterns were reported. Although there are several studies examining histopathology or dermatoscopy of dermatofibromas separately1,5–12 the literature lacks a study investigating both in the same patient group. In the present study, we aimed to analyse histopathological, dermatoscopic and digital microscopic features of dermatofibromas. To the best of our knowledge, this is first report discussing digital microscopic patterns of dermatofibroma.
JEADV 2015, 29, 1958–1966
Methods Two hundred dermatofibromas of 190 consecutive patients from the patient archive of our clinic between August 2013 and June 2014 were retrospectively evaluated and included in the present study. Our hospital is a tertiary health centre in C ß orum which is a province in the Black Sea Region of Turkey. Demographic data, clinical findings and clinical, histopathological, dermatoscopic and digital microscopic images were collected from medical records. Histopathological diagnosis was reviewed according to histopathological features and variants of dermatofibroma reported in the recent studies.3,6,10 We followed the classification consisting of 10 patterns identified by Zaballos et al.5 to group dermatoscopic findings of the cases in our study. We evaluated digital images obtained by a dermatoscope (Dermlite DL-1, 3Gen Inc, San Juan Capistrano, CA, USA) and a handheld digital microscope (Model 44301, Clam Shell, Celestron, LLC,
© 2015 European Academy of Dermatology and Venereology
Features of dermatofibroma
1959
Torrance, CA, USA). Dermatoscopic images were 3264 9 2448 pixels, JPEG formatted with 10-fold magnification and digital microscopic images were 1280 9 1024 pixels, JPEG formatted with 30-fold magnification. Statistical analysis was performed using chi-squaredand Fisher’s exact tests.
Results Demographic and clinical findings
The mean age of the patients was 42.18 13.72 years ranging from 14 to 81 years. Dermatofibromas were more common in females (n = 126, 66.3%) than males (n = 64, 33.7%) and the male to female ratio was 1 : 1.97. Most patients had a solitary lesion (n = 181, 95.3%). Eight patients had two and only one patient had three lesions. The fifth decade was the peak for the women (38.9%) although the highest frequency was in the fourth decade for men (25%) (Fig. 1). Twelve lesions (6%) occurred at the sites of trauma. Most lesions were asymptomatic (82.5%). Pruritus was the most common symptom (12.5%) followed by pain (5.5%). The most common location of dermatofibromas was leg (41%) followed by arm (24%), back (11%) and chest (7.5%) (Fig. 2). Histopathological findings
Histopathological examination revealed nine different dermatofibroma variants. The most frequent variant of dermatofibroma was fibrocollagenous type (n = 98, 49%) followed by sclerotic (n = 38, 19%), histiocytic (n = 26, 13%) and cellular (n = 16, 8%) (Figs. 3–10). The depth of 59.5% of the samples was dermis. Only 6.5% of the lesions reached deep subcutaneous region. Grenz zone was the most common histopathological finding and seen in 89% of the cases. Hyperkeratosis was the most frequent epidermal change in all variants and found in almost all of fibrocollagenous type tumours (94%). Lymphoid nodules in the dermo-subcutaneous junction were observed in 14 cases and most of them were cellular variant (Figs 3–10). Mucin deposition
Figure 2 Distribution of dermatofibroma localizations.
was noted only in histiocytic and fibrocollagenous variants (23.1% and 8.5% respectively) and it was statistically higher in histiocytic variant (P < 0.001) (Table 1). The most frequent histopathological variant of the tumours located on legs was fibrocollagenous (47.5%) followed by sclerotic (28%) and histiocytic (8.5%). Fibrocollagenous variant was also dominant for the localizations of abdomen (100%), arm (68.7%), buttock (50%) and chest (46.7%) although it was not found on the samples from palmoplantar region (Table 2). Dermatoscopic findings
Our cases included eight of ten dermatoscopic patterns that Zaballos et al.5 identified. Half of the cases (50.5%) were in type 2 pattern with peripheral pigment network and central white scar-like patch (Fig. 11). Pattern 2 was the major dermatoscopic appearance (50%) for dermatofibromas located on legs followed by pattern 1 (28%) and pattern 3 (7.3%). It was also the dominant pattern for other certain localizations such as chest (80%), back (50%) and arm (70.8%). Dermatofibromas on face and hands displayed most commonly pattern 1 with total
Figure 1 Age and gender distribution of the cases.
JEADV 2015, 29, 1958–1966
© 2015 European Academy of Dermatology and Venereology
S ß enel et al.
1960
Figure 3 Fibrocollagenous type of dermatofibroma with orthokeratosis, irregular acanthosis and basal pigmentation and predominance of collagen and fibroblasts in a wavy arrangement (H&E, 9100).
Figure 5 Cellular type with high cellularity and short fascicular growth pattern (H&E, 9200).
Figure 6 Aneurysmal type characterized by blood-filled vascular spaces (H&E, 9400). Figure 4 Histiocytic type showing sheets of histiocytes (H&E, 9100).
delicate network located throughout the lesion (40% and 70%, respectively) (Table 3) (Fig. 12). Regarding evaluation of dermatoscopic patterns according to histopathological variants, pattern 2 was the most frequent in fibrocollagenous (47.9%), histiocytic (46.1%), angiomatous (75%) and sclerotic (68.4%) types. Patterns 1 and 2 were found equally in keloidal and cellular variants (40% and 37.5% respectively) (Table 4). In dermatoscopic examination pigment network was the most common feature (n = 133, 66.5%) followed by white scar-like
JEADV 2015, 29, 1958–1966
patch (109, 54.5), brown dots and globules (69, 34.5%) and vascular structures (n = 63, 31.5%). The lowest ratio for pigment network was detected in the sclerotic histopathological variant (0%). Palisading variant lesions showed only dermatoscopic pattern 6 with homogenous pigmentation throughout the lesion (100%). Nearly all tumours with aneurismal and angiomatous variants had vascular features in dermatoscopy (100% and 87.5%, respectively) (Table 4). Digital microscopic findings
Digital microscopy is a non-invasive technique providing 30–100-fold magnification of melanocytic and non-melanocytic
© 2015 European Academy of Dermatology and Venereology
Features of dermatofibroma
1961
Figure 7 Sclerotic type showing hyalinized eosinophilic collagen bundles (H&E, 9200).
Figure 9 Palisading type with verocay-like bodies (H&E, 9100).
Figure 8 Monster type with large, hyperchromatic, bizarre nuclei (H&E, 9400).
Figure 10 Keloidal type with broad, thick and irregularly oriented collagen bundles (H&E, 9100).
skin lesions. A digital microscope is more affordable tool than a dermatoscope. We evaluated a total of 200 dermatofibroma images obtained by a 30-fold magnifying digital handheld microscope. We identified four different types of dermatofibroma in digital microscopy with following features: Type 1: Central scar-like appearance and peripheral pigmentation (Fig. 13) Type 2: Homogenous brown pigmentation (Fig. 14) Type 3: Homogenous-pigmented nodule (Fig. 15) Type 4: Heterogeneous pigmentation with normal-appearing areas (Fig. 16) The most frequent digital microscopic type was type 1 (63%) followed by type 3, 2 and 4 (16%, 13% and 8% respectively).
Type 1 was the prominent pattern in all localizations except for abdomen (Table 5). Type 1 was also most common for all histopathological variants but cellular variant. Digital microscopic examination disclosed type 3 appearance in 68.8% of dermatofibromas with cellular variant (Table 6).
JEADV 2015, 29, 1958–1966
Discussion Although dermatofibromas clinically exhibit the ‘dimple sign’ when laterally squeezed it sometimes may be difficult to distinguish them from certain skin neoplasms such as dermatofibrosarcoma protuberans (DFSP), leiomyosarcoma and amelanotic melanoma. Amelanotic melanoma has more pleomorphism and epidermal involvement with S100 positivity. Dermatofibroma
© 2015 European Academy of Dermatology and Venereology
JEADV 2015, 29, 1958–1966
8 (50.0)
Palisading (2, 1%)
Cellular (16, 8%) 60 (30.0)
6 (37.5)
2 (100)
6 (15.8)
4 (40.0)
0 (0)
2 (25.0)
0 (0)
8 (30.8)
32 (34.0)
18 (9.0)
2 (12.5)
0 (0)
2 (5.3)
0 (0)
2 (100)
4 (50.0)
2 (50.0)
0 (0)
6 (6.4)
2 (40)
94 (47)
Total (100%)
7 (50)
Buttock (7%)
Face (2.5%)
4 (18.2)
Back (11%)
33 (68.7)
2 (100)
Arm (24%)
7 (46.7)
Abdomen (1%)
–
Hand (5%)
Chest (7.5%)
39 (47.5)
–
Leg (41%)
Fibrocollagenous
3 (60)
5 (10.4)
3 (13.6)
5 (33.3)
3 (30)
7 (8.5)
26 (13)
–
–
–
Histiocytic
Histopathological variant
Foot (1%)
Localization (%)
2 (2.4)
8 (4)
–
– 4 (2)
– 1 (2.1)
–
5 (22.7)
– –
–
–
– –
–
2 (20)
–
– 2 (100)
Angiomatous
172 (86.0)
14 (87.5)
2 (100)
30 (78.9)
8 (80.0)
2 (100)
6 (75.0)
2 (50.0)
20 (76.9)
88 (93.6)
Aneurysmal
Table 2 Histopathological variants according to localizations
122 (61.0)
0 (0)
Sclerotic (38, 19%)
Total (200, 100%)
6 (60.0)
30 (78.9)
Keloidal (10, 5%)
2 (25.0)
0 (0)
2 (50.0)
Aneurysmal (4, 2%)
Monster (2, 1%)
18 (69.2)
Histiocytic (26, 13%)
Angiomatous (8, 4%)
56 (59.6)
Hyperkeratosis (%)
Deep subcutaneous (%)
Dermis (%)
Superficial subcutaneous (%)
Epidermal change
Invasion depth
Fibrocollagenous (94, 47%)
Type (n, %)
Table 1 Histopathological features of dermatofibroma variants
2 (1)
–
–
–
–
–
–
–
–
2 (2.4)
Monster
162 (81.0)
16 (100)
2 (100)
32 (84.2)
8 (80.0)
2 (100)
6 (75.0)
2 (50.0)
20 (76.9)
74 (78.7)
Acanthosis (%)
3 (6.2)
3 (30)
4 (4.8)
10 (5)
–
–
–
–
–
–
Keloidal
114 (57)
8 (50)
2 (100)
20 (52.6)
4 (40)
2 (100)
6 (75.0)
2 (50.0)
10 (38.5)
60 (63.8)
2 (4.2)
3 (21.4)
5 (22.7)
3 (20)
38 (19)
–
–
2 (20)
23 (28) –
2 (1)
–
–
1 (7.1)
1 (4.5)
–
–
–
–
–
Palisading
178 (89.0)
14 (87.5)
2 (100)
38 (100)
10 (100)
2 (100)
8 (100)
2 (50.0)
20 (76.9)
82 (87.2)
Sclerotic
Basal Pigmentation (%)
Grenz zone (%)
4 (8.3)
3 (21.4)
4 (18.2)
5 (6.1)
16 (8)
–
–
–
–
–
Cellular
14 (7.0)
6 (37.5)
2 (100)
0 (0)
0 (0)
0 (0)
0 (0)
2 (50.0)
0 (0)
4 (4.3)
Lymphoid nodule (%)
200
5
48
14
22
2
15
10
2
82
Total
14 (7.0)
0 (0)
0 (0)
0 (0)
0 (0)
0 (0)
0 (0)
0 (0)
6 (23.1)
8 (8.5)
Mucin (%)
1962
S ß enel et al.
© 2015 European Academy of Dermatology and Venereology
Features of dermatofibroma
1963
Figure 11 Pattern 2, the most common dermatoscopic pattern of dermatofibromas with peripheral pigment network and central scar-like white patch (dermatoscopy, 910).
Figure 12 Pattern 1, dermatoscopic pattern of dermatofibroma with total delicate network located throughout the lesion (dermatoscopy, 910).
may be confused with leiomyosarcoma and DFSP even in histopathological examination13. Leiomyosarcoma has spindleshaped nuclei, a more uniform fascicular pattern and a more obvious eosinophilic cytoplasm. DFSP lacks cytological polymorphism and epidermal changes and has a tighter fusiform pattern with CD34 positivity.13,14 There are a limited number of studies investigating histopathological and dermatoscopic features of dermatofibromas in the literature.1,5–7,10,11,13,15 As far as we aware, the present study is the first to evaluate both histopathological and dermatoscopic features of dermatofibromas. However, we implemented a preliminary assessment of digital microscopic features of dermatofibroma. Recent reports demonstrated that legs and arms were the most frequent localizations for dermatofibromas like in our study.5,6 The tumours of our patients were much deeper than those in a Korean study by Han et al. and the ratio of dermatofibromas located in deep subcutis was higher (9% vs. 3.3%). Dermatofibromas are composed of fibroblast-like cells, histiocytes and blood cells in histopathology. According to the predominance of three components, three terms ‘nodular subepidermal fibrosis’, histiocytoma’ and ‘sclerosing hemangioma’ were used in the past.16 Although a complete consensus has not been reached at present dermatofibromas are distinguished by their histopathological characteristics.10 Similar to our study Han et al.6 found that fibrocollagenous variant was the most common histopathological type of dermatofibroma (40.1%). Regarding epidermal changes, we found higher percentages of hyperkeratosis (86% vs. 67.2%) and acanthosis (81% vs. 74.4%), and a lower percentage of basal pigmentation (57% vs. 72.1%). Grenz zone was detected in a higher ratio in our study (89% vs. 71.3%) and lymphoid nodules in the dermo-subcutaneous junction and mucin deposition were noted lower (7% vs. 9.8% and 7% vs. 18.9% respectively). In a Portuguese study by Alves et al. lower hyperkeratosis (45%), acanthosis (77%) and basal pigmentation (64%) were detected. Moreover, they found lower percentages of presence of grenz zone (53%) and
Table 3 Dermatoscopic patterns according to localizations Localization (%)
Dermatoscopic pattern Pattern 1
Leg
23 (28.0)
Foot
–
Pattern 2 41 (50) –
Hand
7 (70)
Chest
2 (13.3)
Abdomen
1 (50)
Back
8 (36.4)
2 (20) 12 (80) –
6 (7.3)
Buttock
3 (21.4)
1 (7.1)
8 (16.7)
34 (70.8)
Face
2 (40)
Total
54 (27)
Pattern 4
Pattern 6
Pattern 7
Pattern 8
Pattern 10
Total
3 (3.7)
4 (4.9)
2 (2.4)
2 (2.4)
1(1.2)
–
–
2 (100)
–
–
–
–
–
–
–
–
1 (10)
10
82
15
2
–
1 (6.7)
–
–
–
–
–
–
–
–
1 (50)
–
2
2 (9.1)
–
1 (4.5)
–
–
22
–
9 (64.3)
–
1 (7.1)
–
14
6 (12.5)
–
–
–
–
–
48
11 (50)
Arm
JEADV 2015, 29, 1958–1966
Pattern 3
–
–
–
1 (20)
–
1 (20)
101 (50.5)
14 (7)
5 (2.5)
16 (8)
3 (1.5)
4 (2)
1 (20)
5
3 (1.5)
200
© 2015 European Academy of Dermatology and Venereology
S ß enel et al.
1964
Table 4 Dermatoscopic patterns according to histopathological variants Histopathology (%)
Dermatoscopic pattern Pattern 1
Fibrocollagenous (94, 47%)
Pattern 2
Pattern 8
Pattern 10
Total
8 (8.5)
3 (3.2)
4 (4.2)
2 (2.1)
4 (4.2)
2 (2.1)
94
12 (46.1)
4 (15.4)
–
3 (11.5)
–
–
1 (3.8)
26
2 (50)
2 (50) 2 (25)
–
–
Keloidal (10, 5%)
4 (40)
Sclerotic (38, 19%)
8 (21)
–
–
–
–
–
4
6 (75)
–
–
–
–
–
–
8
2 (100)
–
–
–
–
–
–
2
4 (40)
–
–
–
–
–
10 38
26 (68.4)
–
– 6 (37.5)
Total (200, 100%)
Pattern 7
45 (47.9)
Angiomatous (8, 4%)
Cellular (16, 8%)
Pattern 6
6 (23.1)
Aneurysmal (4, 2%)
Palisading (2, 1%)
Pattern 4
26 (27.6)
Histiocytic (26, 13%)
Monster (2, 1%)
Pattern 3
–
–
3 (7.9)
1 (2.6)
–
–
–
–
2 (100)
–
–
–
2 16
6 (37.5)
54 (27)
2 (12.5)
101 (50.5)
2 (20)
14 (7)
2 (12.5)
–
–
–
–
5 (2.5)
16 (8)
3 (1.5)
4 (2)
3 (1.5)
200
Table 5 Digital microscopic types according to localizations Localization
Digital dermatoscopic type Type 1
Leg Foot
52 (63.4) –
Hand
Type 3
10 (12.2)
16 (19.5)
4 (4.9)
–
–
2 (100)
8 (80)
Chest Abdomen
Type 2
12 (80) –
Back
9 (40.9)
Buttock
2 (20)
–
2 (13.3)
–
2 (100)
–
–
5 (35.7)
Type 4
–
2 (14.3)
7 (50)
7 (14.6)
2 (4.2)
Arm
36 (75)
Face
4 (80)
1 (20)
Total
126 (63)
26 (13)
82 2 10
1 (6.7)
15
6 (27.3)
22
– 7 (31.8)
Total
2
–
14 3 (6.2)
–
–
32 (16)
16 (8)
48 5 200
Table 6 Digital microscopic types according to histopathological variants Histopathology (%)
Digital dermatoscopic type Type 1
Type 2
Type 3
Type 4
Total
Fibrocollagenous (94, 47%)
59 (62.8)
15 (15.9)
11 (11.7)
9 (9.6)
94
Histiocytic (26, 13%)
14 (53.8)
7 (26.9)
3 (11.5)
2 (7.7)
26
Aneurysmal (4, 2%)
3 (75)
–
1 (25)
4
Angiomatous (8, 4%)
6 (75)
–
Monster (2, 1%)
2 (100)
–
Keloidal (10, 5%)
5 (50)
1 (10)
4 (40)
Sclerotic (38, 19%)
31 (81.6)
3 (7.9)
1 (2.6)
Palisading (2, 1%)
2 (100)
–
–
4 (25)
–
11 (68.8)
26 (13)
32 (16)
Cellular (16, 8%) Total (200, 100%)
126 (63)
JEADV 2015, 29, 1958–1966
– 2 (25) –
–
8
–
2
–
10 3 (7.9)
–
38 2
1 (6.2) 16 (8)
Figure 13 Type 1 with peripheral pigmentation and central scarlike appearance (digital microscopy, 930).
16 200
lymphoid nodules (3%). We observed that mucin deposition was statistically higher in histiocytic variant (P < 0.001) although Han et al. reported no difference among the variants. Four major dermatoscopic features of dermatofibroma have been identified in the literature. Arpaia et al. proposed three dermatoscopic types for dermatofibroma: (i) isolated pigment network (31%), (ii) peripheral pigment network associated with globules and dots or with scale crusts and sometimes also with central white patch (13%) and (iii) peripheral pigment network and a central white area (56%).5,15 Only 39 lesions were included in the study by Arpaia et al. and pigment network was found in all dermatofibromas. Therefore, no pattern without pigment network may have been proposed.15 We found a pigment network in 66.5% of the lesions (Table 7). We used dermatoscopic
© 2015 European Academy of Dermatology and Venereology
Features of dermatofibroma
Figure 14 Type 2 with homogenous brown pigmentation (digital microscopy, 930).
Figure 15 Type 3, homogenous-pigmented nodule (digital microscopy, 930).
patterns by Zaballo et al. as the most elaborated classification although we could find no lesion showing pattern 5 and 9. As we experienced in the present study it was hard to distinguish between pattern 8 with peripheral homogeneous pigmentation and central white scar-like patch and pattern 9 with peripheral homogeneous pigmentation and central white network. Digital microscopy was previously used in dermatology practice for the evaluation of morphology of molluscum contagiosum and seborrhoeic keratosis.17,18 Sßenel et al.19 recently
JEADV 2015, 29, 1958–1966
1965
Figure 16 Type 4 with homogenous pigmentation and normalappearing areas (digital microscopy, 930).
reported that digital microscopy increased significantly the diagnostic and therapeutic reliability of teledermatologic application in skin tumours. As far as we are aware, the present study is preliminary to perform an evaluation of the digital microscopic features of dermatofibroma. Dermatofibromas present different clinical appearances in dermatological examination. Fibrocollagenous variant in histopathology, pattern 2 in dermatoscopy and type 1 in digital microscopy were the most common diagnostic styles for dermatofibromas. Although none of the dermatoscopic or digital microscopic style reflected a specific histopathological variant, we found that palisading variant displayed only pattern 6 in dermatoscopy and cellular variant showed type 3 significantly in digital microscopy. Zaballos et al.5 reported that they were not able to elucidate the specificity of each dermatoscopic pattern for the diagnosis of dermatofibroma. As far as we experience, physicians may feel more comfortable with the major patterns, Type 2 dermatoscopic and Type 1 digital microscopic patterns, which reflect typical appearances in the diagnosis of dermatofibroma (Figs 11 and 13). Lesions with type 2 microscopic pattern may be confused with seborrhoeic keratosis (Fig. 14). Seborrhoeic keratosis can be easily distinguished in digital microscopy if the lesion presents milia-like cysts, pseudofollicular (comedo-like) openings, hyperkeratosis and cerebriform appearance. Type 3 microscopic pattern can be also seen in certain nodular lesions such as fibromas, Spitz nevi, dermal nevi or amelanotic melanomas. Histopathological evaluation should be performed for all the lesions with type 3 pattern although clinical examination leads the physician to the diagnosis of dermatofibroma (Fig. 15). Type 4 microscopic pattern
© 2015 European Academy of Dermatology and Venereology
S ß enel et al.
1966
Table 7 Frequency of dermatoscopic features reported in the literature Dermatoscopic feature
Agero et al. (%)12
Arpaia et al. (%)16
Ferrari et al. (%)11
Zaballos et al. (%)5
Pigment network
72
100
83
72
66.5
White scar-like patch
84
>56
92
57
54.5
Brown dots and globules
44
