10.5826/dpc.1401a42
Introduction: Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer. It represents 20% of malignant skin tumors. Dermoscopy is a very useful tool for its diagnosis, which is confirmed by anatomo-pathological study.
Objective: to describe the different dermoscopic structures of cSCC and to investigate their association with clinical form and histopathological grade of differentiation.
Methods: Retro-prospective epidemiological study, collecting patients with squamous cell carcinoma over a period of 5 years. We divided our study population into two groups according to the degree of histological differentiation (well-differentiated and non-well-differentiated) and according to the clinical form (nodulo-ulcerative and nodular) and compared different dermoscopic parameters between these two groups.
Results: Of 72 invasive cSCC, 81.9% were well-differentiated and 18.1% were non-well- differentiated, the clinical form of cSCC was nodulo-ulcerative in 83.3% and nodular in 16.7%. The well-differentiated tumors showed dotted, glomerular and hairpin vessels and the predominance of a white pattern made of centrally distributed keratin as well as white circles, whitish perivascular halo, the distribution of these white structures was radial in nodulo-ulcerarive lesions in contrast to nodular lesions where their distribution as well as that of the keratin was rather diffuse. Non-well-differentiated tumors showed a combined white-red pattern with the predominance of arborizing vessels.
Conclusion:Our results show that dermoscopy can be considered a reliable tool to distinguish between well- and poorly differentiated cSCC, the transition from one to the other is represented by an increase in the amount of mostly arborizing vessels and the decrease in white structures.
text/xml
2160-9381
3460
en
Layla Tahiri
https://creativecommons.org/licenses/by-nc/4.0
Dermatology Practical & Conceptual
Cutaneous squamous cell carcinoma
Cutaneous Squamous Cell Carcinoma: Clinico-Dermoscopic and Histological Correlation: About 72 Cases
Text.Serial.Journal
https://dpcj.org/index.php/dpc
Original Article
2024-01-31
2023-04-24
2024-01-31
2024-02-21
e2024042
Dermatol Pract Concept
Introduction: Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer. It represents 20% of malignant skin tumors. Dermoscopy is a very useful tool for its diagnosis, which is confirmed by anatomo-pathological study.
Objective: to describe the different dermoscopic structures of cSCC and to investigate their association with clinical form and histopathological grade of differentiation.
Methods: Retro-prospective epidemiological study, collecting patients with squamous cell carcinoma over a period of 5 years. We divided our study population into two groups according to the degree of histological differentiation (well-differentiated and non-well-differentiated) and according to the clinical form (nodulo-ulcerative and nodular) and compared different dermoscopic parameters between these two groups.
Results: Of 72 invasive cSCC, 81.9% were well-differentiated and 18.1% were non-well- differentiated, the clinical form of cSCC was nodulo-ulcerative in 83.3% and nodular in 16.7%. The well-differentiated tumors showed dotted, glomerular and hairpin vessels and the predominance of a white pattern made of centrally distributed keratin as well as white circles, whitish perivascular halo, the distribution of these white structures was radial in nodulo-ulcerarive lesions in contrast to nodular lesions where their distribution as well as that of the keratin was rather diffuse. Non-well-differentiated tumors showed a combined white-red pattern with the predominance of arborizing vessels.
Conclusion:Our results show that dermoscopy can be considered a reliable tool to distinguish between well- and poorly differentiated cSCC, the transition from one to the other is represented by an increase in the amount of mostly arborizing vessels and the decrease in white structures.
Layla Tahiri
2024/01/31
10.5826/dpc.1401a42
e2024042
Anatomical pathology laboratory, University Hospital Hassan II, Faculty of Medicine and Pharmacy, Sidi Mohamed Ben Abdellah University, Fez, Morocco
2160-9381
Cutaneous squamous cell carcinoma
en
e2024042
Pyne J, Sapkota D, Wong JC. Squamous cell carcinoma: variation in dermatoscopic vascular features between well and non-well differentiated tumors. Dermatol Pract Concept. 2012;2(4):204a05. DOI: 10.5826/dpc.0204a05. PMID: 23785619. PMCID: PMC3663373.
Cutaneous Squamous Cell Carcinoma: Clinico-Dermoscopic and Histological Correlation: About 72 Cases
https://dpcj.org/index.php/dpc/article/download/3460/2441
        Cutaneous Squamous Cell Carcinoma:
  Clinico-Dermoscopic and Histological Correlation:
                  About 72 Cases
        Sara El-Ammari1, Sara Elloudi1, Hanane Baybay1, Meryem Soughi1, Zakia Douhi1,
          Fatima Zahra Mernissi1, Mohammed Omari2, Samira El fakir 2, Layla Tahiri3


1 Department of Dermatology, University Hospital Hassan II, Faculty of Medicine and Pharmacy, Sidi Mohamed Ben Abdellah University,
  Fez, Morocco
2 Laboratory of Epidemiology, Clinical Research and Community Health- Faculty of Medicine and Pharmacy, Sidi Mohamed Ben Abdellah
  University, Fez, Morocco
3 Anatomical pathology laboratory, University Hospital Hassan II, Faculty of Medicine and Pharmacy, Sidi Mohamed Ben Abdellah
  University, Fez, Morocco



Key words: cutaneous squamous cell carcinoma, dermoscopy, histopathological grade of differentiation, clinical form
Citation: El-Ammari S, Elloudi S, Baybay H, et al. Cutaneous Squamous Cell Carcinoma: Clinico-Dermoscopic and Histological
Correlation: About 72 Cases. Dermatol Pract Concept. 2024;14(1):e2024042. DOI: https://doi.org/10.5826/dpc.1401a42
Accepted: September 24, 2023; Published: January 2024
Copyright: ©2024 El-Ammari et al. This is an open-access article distributed under the terms of the Creative Commons
Attribution-NonCommercial License (BY-NC-4.0), https://creativecommons.org/licenses/by-nc/4.0/, which permits unrestricted
noncommercial use, distribution, and reproduction in any medium, provided the original authors and source are credited.
Funding: None.
Competing Interests: None.
Authorship: All authors have contributed significantly to this publication.
Corresponding Author: Dr El-Ammari Sara, Department of Dermatology, University Hospital Hassan II, Fes, Morocco.
Phone Number: +212 616820719 Email: saraelammari2@gmail.com




  ABSTRACT             Introduction: Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer,
                       accounting for 20% of malignant skin tumors. Dermoscopy is a very useful tool for diagnosing cSCC,
                       and its findings are confirmed through histopathological studies.
                       Objectives: to describe the different dermoscopic structures of invasive cSCC and investigate their
                       association with the clinical form and histopathological grade of differentiation.
                       Methods: We conducted a cross-sectional study, collecting all patients diagnosed with squamous cell
                       carcinoma over a period of 5 years. The study population was divided into two groups based on histologi-
                       cal differentiation (well-differentiated and non-well-differentiated) and clinical form (­ nodulo-ulcerative
                       and nodular). Various dermoscopic parameters were compared between these groups.
                       Results: Out of 72 invasive cSCC, 81.9% were well-differentiated, while 18.1% were non-well- dif-
                       ferentiated. The clinical form of cSCC was nodulo-ulcerative in 83.3% of cases and nodular in 16.7%.
                       Well-differentiated tumors showed dotted, glomerular and hairpin vessels, along with a predominant
                       white pattern characterized by centrally distributed keratin as well as white circles, and whitish peri-
                       vascular halo (P < 0.05). The distribution of these white structures was radial in nodulo-ulcerarive




Original Article | Dermatol Pract Concept. 2024;14(1):e2024042                                                                        1
                     lesions, whereas in nodular lesions, their distribution, as well as that of keratin, was more diffuse
                     (P < 0.05). Non-well-differentiated tumors showed a combined white-red pattern with the predomi-
                     nance of arborizing vessels (P < 0.05).
                     Conclusions: Our results show the reliability of dermoscopy as a tool for distinguishing between
                     well- and poorly differentiated cSCC. This distinction is characterized by an increase in predominantly
                     arborizing vessels and a corresponding decrease in white structures as the tumor progresses from a
                     well-differentiated to a poorly differentiated state. Additionally, the nodulo-ulcerative form exhibits a
                     central distribution of keratin, while the nodular form displays a diffuse distribution.




Introduction                                                      Methods
Cutaneous squamous cell carcinoma (cSCC) is the second            This is a cross-sectional study performed in the d
                                                                                                                   ­ ermatology
most common skin cancer after basal cell carcinoma [1,2].         department of HASSAN II University Hospital, Faculty
It may occur de novo or as a result of precursor lesions [1].     of Medicine and Pharmacy, Sidi Mohamed Ben Abdellah
cSCC accounts for 20% of malignant cutaneous tumors,              ­University of Fez, Morocco. The study extended over a
and its incidence is steadily rising due to population aging      ­period of 5 years, from November 2017 to July 2022.
and increased emphasis on skin cancer screening [2-4]. Der-          The inclusion criteria consisted of patients with skin le-
moscopy has become one of the fundamental diagnostic              sions that were histopathologically confirmed as invasive
techniques in clinical practice, that allows in vivo evalua-      cSCC. Exclusion criteria included patients with poor quality
tion of skin colors and microstructures [5]. The majority of      dermoscopic images, lesions histologically proven to be ker-
dermoscopic structures, including white, vascular and pig-        atoacanthoma or SCC in situ and patients with xeroderma
mented structures have direct histopathologic correlations,       pigmentosum.
making this technique a useful means of communication                Dermoscopic images were captured with a Dermlite DL4
between pathologists and clinicians [6]. The degree of his-       ‘4Gen, at a magnification of 10×, using both polarized and
topathological differentiation in cSCC ranges from good           non-polarized light, with and without immersion. Two in-
to moderate or poor, serving as a significant prognostic          vestigators evaluated the dermoscopic images of all selected
­factor [7]. Poor differentiation is an independent risk fac-     lesions according to predefined criteria [5-10] and which are
tor for metastasis, recurrence, and disease-specific mortality,   presented in Table 1. Additionally, it states that the evalua-
while well-­differentiated SCC is associated with a five-year     tors were blinded to the histology of the lesion when assess-
recurrence-free survival rate of 83% [8]. Thus, early and         ing the dermoscopic features of each lesion.
aggressive management of high-risk cSCC, including poorly            The dermatoscopic evaluation was based on pattern
differentiated tumors, is recommended to reduce mor-              and color analysis, including vessel morphology density
bidity and ­mortality [8]. However, while the dermoscopic         and distribution, as well as the presence or absence of dif-
criteria of cSCC have been well described, there remains a        ferent white structures such as scales, keratin, white cir-
paucity of research examining the correlation between the         cles, white structureless areas, white perivascular halos,
histopathological grade of differentiation. Previous studies      chrysalis and rosettes. The distribution of these structures
have reported that the white pattern predominates in well-­       and the accuracy of the predominant pattern (red, white
differentiated cSCC, while the red pattern is more prevalent      or combined white- red pattern) and the presence of other
in poorly differentiated cSCC. Additionally, there is a scar-     structures like erosions, ulceration and Hemorrhage were
city of studies investigating the correlation between clinical    also assessed.
form and dermoscopic f­ eatures [7].                                 The recruited cases underwent total excision or biopsy
                                                                  and were submitted to routine histopathological confirma-

Objectives                                                        tion using hematoxylin and eosin staining.
                                                                     In this study, cSCC was categorized into two grades of
The aim of this study was to describe the different dermo-        histological differentiation: well and non-well differentiated.
scopic structures of invasive cSCC and investigate their as-      Moderately and poorly differentiated cSCC were evaluated
sociation with clinical form and histopathological grade of       together, due to the small number of cases. The clinical forms
differentiation.                                                  were classified as nodular and nodulo-ulcerative lesions.




2                                                                     Original Article | Dermatol Pract Concept. 2024;14(1):e2024042
              Table 1. Definitions of the criteria used in the evaluation of dermoscopic images.
         Dermoscopic criteria                                                    Definition
 Vascular structures
 Dotted vessels                             Tiny red dots, usually densely distributed next to each other
 Glomerular vessels                         They are usually larger than the dotted vascular structures, they are tortuous
                                            capillaries often distributed in clusters mimicking the glomerular apparatus of the
                                            kidney
 Hairpin vessels                            Vascular loops sometimes twisted and bending
 Linear irregular vessels                   Linear or slightly curved, irregularly shaped vascular structures
 Linear regular vessels                     Linear vascular structures no branches or curves
 Comma vessels                              Coarse vessels that are slightly curved and barely branched
 Arborizing vessels                         Vessels of large diameter that branch irregularly into finest terminal capillaries
 Polymorphous vasculature                   The presence of at least two of the morphological types of vessels described above
 Vessel quantity (> or < 50%)               Vascular structures detected in more or less than half of the lesion surface
 Vessel distribution (radial, diffuse)      Arrangement of vascular structures all over the lesion or at the periphery
 White structures
 Scales/keratin                             White or yellow areas lying on the surface, without any recognizable structure
 Keratin distribution (central, diffuse) Arrangement of keratin in the center or all over the lesion
 White circles                              Roundish structures composed of yellow to light-brown structureless center and
                                            white outer structureless rim
 Whitish structureless areas                Whitish areas not corresponding to scales/keratin, in the absence of any
                                            recognizable structure
 Chrysalis                                  white shiny linear streaks that are seen under polarized dermoscopy. It does not
                                            encompass blotches and strands.
 Rosettes                                   Four closely aggregated white, small dots in correspondence to follicular opening
                                            and resembling 4-leaf clover
 Peri-vascular whitish halo                 White rim surrounding vascular structures
 white structures distribution              Arrangement of white structures all over the lesion, at the periphery or in the
                                            center
 Ulceration                                 Large irregularly shaped or roundish areas of dull red or red-brown structureless
                                            color
 Erosions                                   Small and irregularly distributed orange to red to red-brown structureless areas;
                                            they correspond to superficial hemorrhages and are usually associated with yellow
                                            opaque structures
 Hemorrhage                                 Blood clearly visible in areas covering more than 10% of the lesion surface
 Predominant pattern (white, red or         The color observed in more than 50% of the lesion surface. Combination refers to
 combination)                               the presence of white and red color in almost equal parts of the lesion surface




Statistical Analysis                                                 Results
The data were analyzed using version 26.0 of SPSS for Win-
dows. The mean ± standard deviations for numerical vari-             Patients Demographics, Clinical Characteristics
ables and the number and % values for categorical variables          and Dermatopathological Findings
were given as descriptive statistics. Comparative dermo-             Of 160 histologically confirmed cSCC cases, 88 were ex-
scopic analysis between the different dermoscopic parame-            cluded due to uninterpretable dermoscopic images. A total
ters among the two histological subgroups and the clinical           of 72 cSCC were collected of which 49 were male (68.1%)
forms were performed by chi-square test or Fisher exact test         and 23 were females (31.9%), the mean age at diagnosis was
depending on the sample size of the parameter to compare.            68.67 years with extremes (25- 1). Concerning the origin 46
For multivariate analysis, binary logistic regression was            of our patients (63.9%) came from an urban environment,
used. Values of P less than 0.05 were accepted as significant.       while 26 (36.1%) from a rural environment. Chronic sun




Original Article | Dermatol Pract Concept. 2024;14(1):e2024042                                                                    3
exposure was reported in 49 patients (68.1%) and 5 patients            with comparable percentages (Table 2) without statistically
had a history of skin cancer (6.9%). Based on the origin of            significant difference (P > 0.05)
lesions, 54 (75%) lesions were de novo; 7 patients (9.7%)
had developed cSCC on a burn scar, 6 (8.3%) on a chronic               Correlation Dermoscopy-Clinical Form
                                                                       (Tables 4 and 5)
wound, 4 (5.6%) on a lichen and in one patient (1.4%) on
hereditary epidermal bullosa. Associated actinic keratosis             The most observed dermoscopic aspects in nodulo-ulcerative

lesions diagnosed through clinical examination and der-                variant (Figure 4) were: opaque yellowish scales (N = 52;

moscopy were found in 16 patients (22.2%). In our series               86.7%), hemorrhagic spots (N = 54; 90.0%), the presence of

57 patients (79.2%) consulted at the tumor stage, while the            ulceration (N = 60; 100% OR = 0.015 [0.001; 0.178]), the

remaining patients consulted at an earlier stage. Clinically,          central distribution of keratin N = 39; 72.2% OR = 11.120

49 patients had a phototype IV (68.1%) and 20 had a pho-               [1.184; 104.483]) and the radial distribution of different

totype III (27.8%). The frequency distribution of the lesions          white structures with a predominance of the white pattern

across various sites was as follows: cervicocephalic extrem-           (N = 36; 60%). All these dermoscopic aspects showed a sta-

ity (N = 32; 44.4%), lower limbs (N = 26; 36.1%), oral                 tistically significant correlation with the nodulo-ulcerative

mucosa (N = 7; 9.7%), genital mucosa (N = 4, 5.6%) and                 form, with a Pvalue < 0.05. Other aspects were also pre-

upper limbs (N = 3; 4.2%). The clinical form of cSCC was               dominant in this form, but the correlation was statistically

nodulo-ulcerative in 60 patients (83.3%) and nodular in
­                                                                      non-significant, such as hairpin vessels (N = 42; 70%), whit-

12 patients (16.7%). The mean size of the lesions was                  ish structureless areas (N = 47; 78.3%) and peri-vascular

6.52 cm. According to the histopathological grade of differ-           whitish halo (N = 41; 68.3%).

entiation, 59% or 81.9% of the cSCC lesions were well dif-                Concerning the nodular form (Figure 3), the distribution

ferentiated and 13% or 18.1% were non-well differentiated.             of keratin and different white structures was diffuse, with per-
                                                                       centages of (N = 7; 70.0%) and (N = 9; 75.0%) respectively,
                                                                       with the predominance of the white-red pattern, being statis-
Dermatoscopic Analysis
                                                                       tically significant (P < 0.05) for each feature. However, the
The analysis of different dermoscopic structures in SCC, ac-
                                                                       presence of comma vessels, arborizing vessels and regular lin-
cording to the clinical form and histopathological grade of
                                                                       ear vessels was more present in this form, with percentages of
differentiation in our series, is presented in Tables 2, 3, 4 and 5.
                                                                       33.3%, 50.0% and 25.0% respectively. However, the P value
Correlation Dermoscopy-Histopathological                               for these features was > 0.05, indicating a ­
                                                                                                                   non-significant
Differentiation Grade (Tables 2 and 3)                                 correlation.
The most observed dermoscopic aspects in well-­differentiated
cSCC (figure1) were: dotted vessels (N = 44 ,74.6%), glomer-
                                                                       Conclusions
ular (N = 36 ,61%), hairpin (N = 44, 74.6%), whitish scales
(N = 44, 74.6%), yellowish scales (N = 51 ,86.4%), keratin             The incidence of cutaneous squamous cell carcinoma (cSCC)
(N = 56, 94.9%) with central distribution (N = 39, 69.6%),             has been increasing worldwide for several decades and is es-
white circles (N = 44, 74.6%), whitish structureless areas             timated to be 15 to 35/100,000 people per year [2]. It is
(N = 49, 83.1%), perivascular whitish halo (N = 41, 69.5%)             more common in males than in women and affects the older
with a predominance of the white pattern (N = 38, 64.4%)               population (80% of cases are in adults over 60), due to the
and < 50% of vascular structures. All these dermoscopic as-            correlation with cumulative sun exposure [3]. The epidemio-
pects were significantly correlated with well-­differentiated          logical characteristics of the patients in our study are consis-
cSCC (P < 0.05).                                                       tent with previous data.
    For non-well differentiated cSCC (Figures 2 and 3), ar-               Invasive cSCC can develop de novo, or from ­pre-cancerous
borizing vessels were the most common dermoscopic feature              lesion or certain chronic inflammatory skin areas, such as
(N = 9; 69.3%) and was associated with a higher risk of                chronic wounds, burns, scars, ulcers etc [3,4], as was the case
developing non well differentiated squamous cell carcinoma             in some of our patients.
OR = 14.8 [2.43; 90.37]. The other dermoscopic features                   Dermoscopy is an essential in-vivo, non-invasive diagnos-
that exhibited a statistically significant difference in non-well      tic method that provides the visualization of morphological
differentiated SCC included a vessel quantity higher than              characteristics not detectable with the naked eye [11]. Only
50% (N = 9; 69.3%) with a predominance of the combined                 a limited number of studies have been conducted primarily
white-red pattern (N = 8, 61.5%).                                      focusing on the correlation between degree of differentiation
    Linear irregular vessels, vascular polymorphism, rosettes,         and dermoscopy.
chrysalis, presence of ulceration and hemorrhagic spots were              In this study, we identified useful clues that may sug-
present in both well- and non-well-differentiated groups               gest the degree of differentiation of cSCC. The presence of



4                                                                          Original Article | Dermatol Pract Concept. 2024;14(1):e2024042
  Table 2. Comparison of dermoscopic aspects according to histopathological differentiation grade.
                                                                       DIFFERENTIATION GRADE
                                               Well differentiated               Non-well differentiated
   DERMOSCOPIC STRUCTURES                            N = 59                             N = 13                          P-value
 Vascular structures
 Dotted vessels                                     44 (74.6%)                           5 (38.5%)                       .016
 Glomerular vessels                                  36 (61%)                            3 (23.1%)                       .014
 Hairpin vessels                                    44 (74.6%)                           5 (38.5%)                       .016
 Comma vessels                                       9 (15.3%)                           4 (30.8%)                       .176
 Linear irregular vessel                            50 (84.7%)                           11 (84.6%)                      .637
 Linear regular vessel                               8 (13.8%)                            0 (0.0%)                      0.180
 Arborizing vessels                                 11 (18.6%)                           9 (69.3%)                       .001
 Polymorphous vasculature                           54 (91.5%)                           12 (92.3%)                      .705
 Quantity of vessels                                                                                                     .004
 <50%                                               44 (74.6%)                           4 (30.8%)
 >50%                                               15 (25.4%)                           9 (69.3%)
 Vessels distribution                                                                                                    .448
 Radial                                             19(32.2%)                            5 (38.5%)
 Diffuse                                            40 (67.8%)                           8 (61.5%)
 White structures
 Whitish scales                                     44 (74.6%)                           5 (38.5%)                       .016
 Opaque yellow scales                               51 (86.4%)                           7 (53.8%)                       .015
 Keratin                                            56 (94.9%)                           8 (61.5%)                       .004
 Keratin distribution                                                                                                    .045
 Central                                            39(69.6%)                            3 (37.5%)
 Diffuse                                            17 (30.4%)                           5 (62.5%)
 White circles                                      44 (74.6%)                           4 (30.8%)                       .004
 Whitish structureless areas                        49 (83.1%)                           5 (38.5%)                       .002
 Chrysalis                                          21 (35.6%)                           4 (30.8%)                       .505
 Rosettes                                           26 (44.1%)                           6 (46.2%)                       .565
 Peri-vascular whitish halo                         41 (69.5%)                           5 (38.5%)                       .039
 White structures distribution                                                                                           .327
 Central                                             6 (10.2%)                            1 (7.7%)
 Radial                                             30 (50.8%)                           4 (30.8%)
 Diffuse                                            23 (39.0%)                           8 (61.5%)
 Erosion                                               0 (0%)                             1 (7.7%)                       .181
 Ulceration                                         51 (86.4%)                           12 (92.3%)                      .486
 Hemorrhage                                         52(88.1%)                            9 (69.2%)                       .103
 Predominant pattern                                                                                                     .022
 White                                              38 (64.4%)                           3 (23.1%)
 Red                                                  3 (5.1%)                           2 (15.4%)
 White and red                                      18 (30.5%)                           8 (61.5%)




previously described white structures, including scales, cen-        present in non-well-differentiated cSCC. This finding aligns
trally distributed keratin, white circles, perivascular whitish      with the results reported by Saleh HM et al, Lallas et al, and
halo and whitish structureless areas were strongly associated        Zalaudek et al reported that these whitish structures were as-
with well-differentiated cSCC, while the diffuse distribution        sociated with well- or moderately differentiated variants and
of keratin and other white structures were more likely to be         that a central distribution of scales or keratin was associated



Original Article | Dermatol Pract Concept. 2024;14(1):e2024042                                                                    5
with a 36-fold reduced possibility for poor differentiation           deeper than well differentiated lesions. This deeper invasion
[7,8,12]. In the latter, signs of keratinization are not found        may account for the higher prevalence of linear and branch-
[8,12,13], while the moderately differentiated variant would          ing vessels, which are more commonly observed as tumors
show less expression of dermoscopic white indices compared            increase in thickness and contribute to tumor development.
to the well differentiated cSCC [7].                                      Our results are not in agreement with those of Saleh
    The vascular findings observed in our analysis of                 et al [7], who documented that well-differentiated lesions
well-differentiated tumors are characterized by dotted, glo-          had a higher incidence of linear irregular vessels followed
merular, and hairpin vessels, with the presence of a whitish          by glomerular vessels and hairpin vessels. According to Lal-
perivascular halo. In contrast, non-well differentiated tu-           las et al [13], well-differentiated cSCC is characterized by
mors exhibited predominantly branched or arborizing ves-              elongated peripheral vessels reminiscent of the arborescent
sels. These findings are consistent with the results of Pyne          vessels of basal cell carcinoma, while poorly differentiated
et al [14], who also demonstrated through their study that            cSCC shows a polymorphic vascularization. Similar obser-
non-well differentiated tumors tended to be histologically            vations were made by Zalaudek [12] in poorly differenti-
                                                                      ated squamous cell carcinoma, where a reddish background
                                                                      accompanied small-caliber linear vessels, hairpin vessels, or
  Table 3. Results of the multivariate analysis
                                                                      glomerular vessels. In contrast, the well-differentiated sub-
of the correlation between dermoscopic features
                                                                      type primarily exhibited hairpin and dot vessels.
     and histological differentiation grade.
                                                                          We found that the quantity of vessels was significantly
                                              Confidence              correlated with the degree of differentiation, which is consis-
                          Odds ratio         interval 95%
                                                                      tent with the results of Lallas et al [8]. They reported that tu-
 Arborizing vessels           14.8            [2.43; 90.37]           mors with over 50% of the lesion area covered by vessels had
 White circles                .033           [0.003; 0.356]           a 30- to 120-fold higher possibility of being poorly differen-
 Whitish                      .031           [0.003; 0.331]           tiated. They also added that vessel caliber was also found to
 structureless areas                                                  be a significant predictor of degree of differentiation, since




     Figure 1. A) Nodulo-ulcerative well-differentiated squamous cell carcinoma located in the cheek. (B) Dermoscopy reveals a pre-
     dominantly white pattern, white circles, rosettes, whitish structureless areas, dotted and glomerular vessels with <50% of vascular
     structures, ulceration.



6                                                                          Original Article | Dermatol Pract Concept. 2024;14(1):e2024042
  Figure 2. (A) Moderately differentiated nodule ulcerative tumor of the nose. (B) Dermoscopy shows a combined white-red pattern, ro-
  settes, chrysalis, keratin, hemorrhage, arborescent and linear irregular vessels radially arranged.




 Figure 3. (A) Poorly differentiated Nodular tumor of the cheek. (B) Dermoscopy shows a red pattern, polymorphic vasculature diffusely
 distributed over > 50% of the tumor surface, made of arborescent, linear irregular vessels and comma vessels, whitish structureless areas,
 whitish scales with diffuse distribution.



a small caliber vessel had a threefold higher probability of            probability of a poorly differentiated cSCC [8]. These results
poor differentiation while those with large caliber vessels             are consistent with ours and those of Saleh et al [7].
had an 83% lower probabilities of being poorly differen-                    Concerning the correlation of dermoscopic aspects and
tiated [8]. Lallas et al also revealed that the presence of a           the clinical form, to the best of our knowledge, only one
predominantly red color, attributed to the absence of des-              study has investigated this correlation. This gap in the lit-
quamation and keratin and the presence of bleeding and/or               erature motivated our research, as we aim to contribute
dense vasculature, was in favor of poor differentiation, while          significantly to the field. Saleh et al [7] examined 17 le-
a predominantly white or white-yellow color reduced the                 sions representing three clinical forms of cSCC: nodular,



Original Article | Dermatol Pract Concept. 2024;14(1):e2024042                                                                            7
                    Table 4. Comparison of dermoscopic aspects according to clinical form.
                                                                            CLINICAL FORM
                                                    Nodulo-ulcerative                       Nodular
       DERMOSCOPIC STRUCTURES                              N = 60                            N = 12                  P-value
 Vascular structures
 Dotted vessels                                          41 (68.3%)                        8 (66.7%)                  .578
 Glomerular vessels                                      33 (55.0%)                         6 (50%)                   .498
 Hairpin vessels                                         42 (70.0%)                        7 (58.3%)                  .318
 Comma vessels                                           9 (15.0%)                         4(33.3%)                   .137
 Linear irregular vessel                                 51(85.0%)                        10 (83.3%)                  .587
 Linear regular vessel                                    5(8.5%)                          3(25.0%)                   .127
 Arborizing vessels                                      14(23.3%)                         6(50.0%)                   .067
 Polymorphous vasculature                                55 (91.7%)                       11(91.7%)                   .680
 Quantity of vessels                                                                                                  .157
 <50%                                                    42(70.0%)                         6 (50.0%)
 >50%                                                    18(30.0%)                         6 (50.0%)
 Vessels distribution                                                                                                 .378
 Radial                                                  21 (35.0%)                        3(25.0%)
 Diffuse                                                 39 (65.0%)                        9(75.0%)
 White structures
 Whitish scales                                          42(70.0%)                         7(58.3%)                   .318
 Opaque yellow scales                                    52 (86.7%)                        6(50.0%)                    .009
 Keratin                                                 54 (90.0%)                       10(83.3%)                    .399
 Keratin distribution                                                                                                  .015
 Central                                                 39 (72.2%)                        3 (30.0%)
 Diffuse                                                 15 (27.8%)                        7(70.0%)
 White circles                                           39 (65.0%)                        9 (75.0%)                   .378
 Whitish structureless areas                             47(78.3%)                         7(58.3%)                    .138
 Chrysalis                                               20(33.3%)                         5(41.7%)                    .404
 Rosettes                                                27 (45.0%)                        5 (41.7%)                   .545
 Peri-vascular whitish halo                              41 (68.3%)                        5 (41.7%)                   .079
 White structures distribution                                                                                         .043
 Central                                                  6 (10%)                           1 (8.3%)
 Radial                                                  32(53.3%)                         2(16.7%)
 Diffuse                                                 22(36.7%)                         9 (75.0%)
 Erosion                                                  1(1.7%)                           0(0.0%)                    .833
 Ulceration                                              60 (100%)                           0(0%)                     .000
 Hemorrhage                                              54 (90.0%)                        7(58.3%)                    .015
 Predominant pattern                                                                                                   .025
 White                                                   36 (60.0%)                        4 (33.3%)
 Red                                                      2 (3.3%)                         3 (25.0%)
 White and red                                           22 (36.7%)                        5(41.7%)




nodulo-ulcerative, and ulcerative. They found that nodular       less than 50% for the nodular form. In our study, linear ir-
and nodulo-ulcerative lesions showed mainly linear irregular     regular vessels were the most frequently observed, followed
vessels followed by glomerular vessels. In ulcerative lesions,   by dotted vessels and then glomerular vessels in both stud-
glomerular vessels dominated, with a vessel quantity greater     ied forms, Additionally, we found a higher presence of hair-
than 50% for nodulo-ulcerative and ulcerative tumors and         pin vessels in the nodulo-ulcerative form and an increased



8                                                                     Original Article | Dermatol Pract Concept. 2024;14(1):e2024042
occurrence of arborescent vessels in the nodular form, with              significantly associated with moderately differentiated cSCC.
a vessel quantity less than 50% in the nodulo-ulcerative tu-             This association between clinical form and degree of differ-
mors, contrary to the above results. For whitish structures,             entiation was not investigated in our study.
whitish perivascular halo and whitish structureless areas                    The main limitation of our study is the combined analy-
were present in both forms, but more found in the nodu-                  sis of non-well-differentiated tumors, which was due to the
lo-ulcerative form. Nodular lesions exhibited a dominant                 small number of poorly differentiated (N = 3) and moderately
presence of white circles, along with a diffuse distribution             differentiated (N = 10) cSCC. In addition, the dermoscopic
of keratin. In contrast, the nodulo-ulcerative form showed a             images were interpreted retrospectively, which introduces a
central distribution of keratin. These results were not consis-          potential bias. However, it is important to emphasize that we
tent with those of Saleh et al [7], who detected a central dis-          applied rigorous criteria in the selection process, excluding
tribution of keratin in both nodular and nodulo-ulcerative               any images of poor quality. As a result, the number of cases
forms, the presence of white circles in all nodular lesions and          included in the analysis was reduced.
in more nodulo-ulcerative than ulcerative lesions with the                   Our study highlights the potential of dermoscopy as a
absence of perivascular whitish halo in the latter form and              non-invasive technique to provide clinicians with valuable
its presence in the other two forms.                                     insights into the histopathological differentiation of SCC.
    In the same study [7], they concluded that nodular and               In addition, our study emphasizes the importance of collab-
nodulo-ulcerative lesions were significantly associated with             oration between clinicians and anatomopathologists when
well-differentiated cSCC, whereas ulcerative lesions were                an immunohistochemical complement is required, particu-
                                                                         larly in cases of poorly differentiated tumor proliferation.
                                                                         By engaging in discussions and considering immunohisto-
  Table 5. Results of the multivariate analysis
                                                                         chemical markers specific to poorly differentiated squa-
of the correlation between dermoscopic features
                                                                         mous cell carcinomas, particularly when a dermoscopic
                and clinical form.
                                                                         red pattern with a predominance of arborizing vessels is
                             Odds              Confidence                visualized. This collaborative approach not only improves
                             ratio            interval 95%
                                                                         patient care but also carries economic benefits by optimiz-
 Keratin distribution       11.120          [1.184; 104.483]
                                                                         ing the selection and utilization of immunohistochemical
 ulceration                  0.015            [0.001; 0.178]             resources.




        Figure 4. (A) Nodulo-ulcerative Well-differentiated squamous cell carcinoma located in the cheek. (B) Dermoscopy reveals a
        predominantly white pattern, central mass of keratin, whitish scales, chrysalis, radial arrangement of linear irregular vessels
        and hairpin vessels surrounded by a whitish halo.



Original Article | Dermatol Pract Concept. 2024;14(1):e2024042                                                                            9
     Our results show that dermoscopy can be considered                    Rep. 2015;9(4):89-97. DOI: 10.3315/jdcr.2015.1221. PMID:
a reliable tool to distinguish between well- and poorly dif-               26848316. PMCID: PMC4733351.
                                                                      6.   Yélamos O, Braun RP, Liopyris K, et al. Dermoscopy and der-
ferentiated cSCC. This distinction is characterized by an
                                                                           matopathology correlates of cutaneous neoplasms. J Am Acad
increase in predominantly arborizing vessels and a cor-
                                                                           Dermatol. 2019;80:341-363. DOI:10.1016/j.jaad.2018.07.073.
responding decrease in white structures as the tumor pro-                  PMID: 30321581.
gresses from a well-differentiated to a poorly differentiated         7.   Saleh HM, Mokhtar MM, Mostafa AE. Dermoscopic criteria of
state. Moreover, the nodulo-ulcerative form demonstrates a                 squamous cell carcinoma in relation to clinical variant and histo-
central distribution of keratin, while the nodular form dis-               pathologic differentiation grade. J Egypt Womens Dermatol Soc.
                                                                           2020;17:83-90. DOI: 10.4103/JEWD.JEWD_5_20
plays a diffuse distribution. Dermoscopy not only aids in
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­accurate diagnosis but also provides valuable guidance to the
                                                                           features of invasive cutaneous squamous cell carcinoma depend
­
anatomo-pathologist. Additionally, the implementation of                   on the histopathological grade of differentiation. Br J Derma-
dermoscopy offers economic benefits by streamlining the di-                tol 2015; 172:1308–1315. DOI: 10.1111/bjd.13510. PMID:
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tient management, ultimately leading to improved prognosis.           9.   Zalaudek I, Giacomel J, Schmid K, et al. Dermatoscopy of facial
                                                                           actinic keratosis, intraepidermal carcinoma, and invasive squa-
     Further studies are desirable to investigate the associa-
                                                                           mous cell carcinoma: a progression model. J Am Acad Dermatol.
tion between the different dermoscopic criteria and clinical
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10                                                                         Original Article | Dermatol Pract Concept. 2024;14(1):e2024042
