Report

The role of reflectance confocal microscopy in the diagnosis

and management of squamous cell carcinoma in situ treated
with photodynamic therapy
Yee L. Teoh, MBBS, MRCP, Ling Y. Kuan, MBBS, MRCP, Wei-Sheng Chong, MBSS, FRCP,
Hui Y. Chia, MBBS, MRCP, Tien G.S. Thng, MBSS, FRCP and Sai Y. Chuah, MB, ChB, MRCP

National Skin Centre, Singapore, Abstract

Singapore, and Department of Background Reflectance confocal microscopy (RCM) is increasingly used for noninvasive
Dermatology, Changi General Hospital,
in vivo diagnosis of skin cancers. We seek to determine if RCM is useful for the diagnosis and
Singapore, Singapore
follow-up of squamous cell carcinoma in situ (SCCIS) posttreatment to document clearance.
Correspondence Methods A pilot prospective study enrolled 10 patients with a total of 11 SCCIS lesions.
Sai Y. Chuah, MB, CHB, MRCP Clinical, confocal, histological features and fluorescence diagnosis (FD) were recorded pre-
National Skin Centre and posttreatment.
1 Mandalay Road
Results Four SCCIS lesions underwent RCM imaging prior to biopsy, while 11 SCCIS
308205 Singapore
Singapore
lesions were followed up with RCM imaging. Clinical features of persistent SCCIS post-PDT
E-mail: sychuah@nsc.com.sg in four out of 11 follow-up cases were confirmed with RCM and FD. There were no RCM
features of SCCIS in seven lesions which were clinically cured. All eight (four new SCCIS and
Funding: None. four follow-up) cases displayed atypical honeycomb pattern. Two cases (25%) showed
numerous epidermal dendritic cells, while small bright refractive cells were present in the
Conflicts of Interest: None.
epidermis in two lesions (25%). Round blood vessels in the superficial dermis were seen in
doi: 10.1111/ijd.14581
four lesions (50%), while three lesions (37.5%) showed dermal inflammatory cells.
Conclusion There was good correlation between histological and confocal features in patients
who underwent RCM imaging prior to biopsy. RCM may be a complementary tool in diagnosing
SCCIS and to monitor response to nonsurgical treatment by avoiding unnecessary biopsies
especially in lesions with persistent residual postinflammatory erythema.

photodynamic therapy, cryotherapy, imiquimod, and 5-fluo-

Introduction
Squamous cell carcinoma in situ (SCCIS) is a common superfi-
cial skin cancer, most commonly occurring on sun-exposed
regions. They commonly present as a pink or erythematous
macule or patch with variable pigmentation and scaling on the
surface. The risk of invasive carcinoma for SCCIS lesions is
estimated to be between 3 and 5%,1–3 except for special sites
such as the penis, in which the risk of invasion approximates
10%. SCCIS may be associated with chronic human papillo-
mavirus infection, especially lesions occurring on the fingers
and fingernails which may present as an erythronychia, ony-
cholysis, nail dystrophy, or verrucous periungual tumors.4,5 A
history of chronic arsenic ingestion is a risk factor for multiple
SCCIS and invasive squamous cell carcinoma (SCC).6 In view
of its relatively low risk of invasive carcinoma, dermatologists
may recommend a variety of therapeutic choices for patients
with SCCIS, especially in patients who are in favor of noninva-
sive treatment or those who are not suitable for surgery. The
1382 established nonsurgical treatment options for SCCIS include
rouracil cream. Some patients who prefer nonsurgical treatment
may also choose to have noninvasive monitoring such as reflec-
tance confocal microscopy (RCM) to avoid repeated skin biop-
sies examining recurrence or persistent residual tumor after
initial treatment. In our experience, our patients with Asian-type
skin may have persistent postinflammatory erythema despite
complete clearance of the SCCIS, while nonscaly pigmented
patches may not always represent resolution of their SCCIS,
making RCM a helpful modality to identify the presence of resid-
ual SCCIS.
We aim to evaluate the use of RCM imaging in the diagnosis
and monitoring of patients who underwent nonsurgical treatment
for SCCIS in a 24-month follow-up study.
Materials and methods
A pilot study of the use of RCM on new and follow-up cases of
SCCIS was performed. The aim of the study was to evaluate
the usefulness of RCM in diagnosing, detecting residual atypia

International Journal of Dermatology 2019, 58, 1382–1387 ª 2019 The International Society of Dermatology
Teoh et al.
following photodynamic therapy (PDT), and monitoring
recurrence of SCCIS in our skin cancer clinic. From September
to December 2014, we recruited patients with a clinical
diagnosis of a newly diagnosed SCCIS or those under follow-up
for SCCIS following PDT in our skin cancer clinic at the
National Skin Centre, Singapore.
Clinically suspicious lesions of SCCIS based on clinical and
dermoscopic findings underwent RCM imaging before biopsy.
Patients with histologically confirmed SCCIS lesions who were
treated with PDT were subsequently imaged to assess for
complete clearance at 3 months and to monitor for recurrence at
6, 9, 12, 18, and 24 months in our skin cancer clinic. In patients
who did not have complete clinical or confocal clearance at
3 months or showed signs of recurrence during visits at 6, 9, 12,
18, and 24 months, the clinician would re-discuss surgical and
nonsurgical treatment options. Those who opted for nonsurgical
treatment will be re-imaged with RCM at each follow-up visit.
The lesions were imaged with the Vivascope device 1500,
Lucid Inc, Rochester, NY. A standardized imaging procedure by
capturing a series of images was performed for all cases.
Horizontal mapping of 494 mm (Vivablock) was captured at
various levels of the skin, from the stratum granulosum to the
superficial dermis (4 9 4 mm to 6 9 6 mm). Vertical mapping
with images of a size of 0.5 9 0.5 mm was performed using
the Vivastack function in 4–5 lm steps to a maximum depth of
200 lm, starting at the stratum corneum and continuing
throughout the epidermis and papillary dermis. Individual
images were taken during the imaging process at regions of
special interests.
All 10 patients (total of 11 lesions) underwent skin biopsy to
confirm the diagnosis of SCCIS before PDT. There was no
breach of the epidermis in any of the 11 lesions. For the four
patients who underwent RCM examination prior to biopsy to
confirm SCCIS, the biopsies were performed at the same site
of RCM examination for histopathologic analysis. The tissue
was fixed in formalin and embedded in paraffin. A
dermatopathologist recorded the pathological changes observed
for all lesions biopsied. Written consent was obtained from all
patients before the skin biopsies.
A 1-mm thick layer of methyl aminolevulinate (MAL) cream
(Metvix 160 mg/g; Photocure ASA, Hoffsveien 48, NO-0377,
Oslo, Norway) was applied to each lesion and subsequently
covered with an occlusive dressing for 3 hours. The dressings
were removed after 3 hours and the cream washed off with
0.9% saline solution before illumination with red light using a
light-emitting diode lamp (Aktilite CL128, PhotoCure ASA,
Hoffsveien 48, NO-0377, Oslo, Norway) at 570–670 nm (peak
wavelength at 630 nm). The total irradiation dose was 37 J/cm2
at 8 cm lamp-skin distance, with a lamp irradiance of 75 mW/
cm2. This process was then repeated a week later. All patients
underwent the same treatment protocol.
In the event that patients showed either clinical recurrence or
RCM changes consistent with recurrence or unresolved SCCIS
ª 2019 The International Society of Dermatology
RCM in the diagnosis and monitoring of SCCIS Report 1383
at any point during the study, they would undergo fluorescence
diagnosis (FD) in our clinic. FD is a registration of the
fluorescence emitted by tissue after application of a
photosensitizer, indicating the presence of tumoral cells. It is a
valid diagnostic tool for the follow-up of actinic keratoses,
SCCIS, and invasive SCC with the advantage of avoiding
unnecessary posttreatment biopsies.7,8
Results
Ten patients with a total of 11 biopsy-proven SCCIS lesions were
evaluated with RCM. Nine patients were of Chinese ethnicity with
Fitzpatrick skin types III and IV. One patient was a Caucasian
man with Fitzpatrick skin type II. The lesions were located on the
head and neck region in 18.2% (n = 2), upper limbs in 18.2%
(n = 2), lower limbs in 36.4% (n = 4), and trunk in 27.3% (n = 3).
Apart from one patient who had a history of recurrent skin cancer
due to previous arsenic exposure, none had any known risk of
immunosuppression or history of viral warts.
Four patients underwent RCM imaging prior to the biopsy,
while all 11 lesions were re-imaged during every follow-up visit
after treatment. All underwent PDT as part of their treatment for
SCCIS with seven lesions showing complete resolution at
3 months follow-up while four lesions had persistent SCCIS
based on clinical and RCM imaging. Of the patients who had
persistent SCCIS at 3 months follow-up visit, one patient contin-
ued another three sessions of PDT followed by 5-fluorouracil
cream 5%, one patient had an additional two sessions of PDT,
and two patients were subsequently treated with cryotherapy.
Table 1 shows the clinical, confocal, and histological features at
presentation and their 12–30 months follow-up visit, treatment
modalities, and recurrence of SCCIS if any. Table 2 describes
the RCM findings for newly diagnosed SCCIS prior to skin
biopsy, while Table 3 depicts the RCM findings of the 11
lesions, of which four out of 11 SCCIS lesions persisted at
3 months post-PDT, and patients 2 and 10 demonstrated recur-
rence at 7 and 11 months, respectively.
On RCM imaging, all eight (four new SCCIS and four persis-
tent SCCIS on follow-up) lesions displayed atypical honeycomb
with disarray pattern in the epidermis. Two out of eight lesions
(25%) showed the presence of numerous dendritic cells in the
epidermis (Fig. 2b), while small bright refractive cells were seen
in the epidermis in two out of eight lesions (25%). Round blood
vessels in the superficial dermis were seen in four lesions
(50%), while three lesions (37.5%) showed inflammatory cells in
the dermis. Figures 1 and 2 show the baseline and follow-up
clinical, confocal, fluorescence diagnosis, and initial histopatho-
logical findings confirming the diagnosis of SCCIS in two
patients in our study.
One of the four patients with persistent SCCIS after the initial
two PDT sessions was patient 1 with a penile SCCIS. He was
advised to undergo surgical excision in view of his slow clinical
improvement in a high-risk location despite another five
International Journal of Dermatology 2019, 58, 1382–1387
 1384
Report

Table 1 Summary of the initial and follow-up clinical presentation, confocal findings, and histopathological features and the treatment received by all patients in our
study

Patient no (lesion no) 1 2 3 (i) 3 (ii) 4 5 6 7 8 9 10

Demographic: Age/ 76, Caucasian, male 61, Chinese, female 91, Chinese, female 91, Chinese, female 73, Chinese, female 75, Chinese, female 88, Chinese, 72, Chinese, male 62, Chinese, female 49, Chinese, female 74, Chinese,
gender/ethnicity female female
Location Penis Right elbow Right shin Left index finger Right temple Back Left temple Chest Left lateral calf Left thigh Right fourth
toe
Clinical features 40 9 40 mm moist 15 9 10 mm scaly 15 9 10 mm scaly 6 9 6 mm 6 9 10 mm scaly 20 9 18 mm scaly 15 9 15 mm 35 9 30 mm scaly, 8 9 5 mm 20 9 14 mm well- 25 9 25 mm
red patch on the pink plaque pink plaque hyperkeratotic plaque erythematous scaly brown erythematous hyperkeratotic defined scaly nonhealing
glans and adjacent plaque with plaque plaque plaque with brown plaque left erythematous ulcer
RCM in the diagnosis and monitoring of SCCIS

foreskin surrounding irregular edge and lateral calf plaque on left thigh

International Journal of Dermatology 2019, 58, 1382–1387

erythematous scaly mild crusting on
patch edges
RCM done pre-treatment No Yes Yes Yes Yes No No No No No No
Histological diagnosis SCCIS SCCIS SCCIS SCCIS SCCIS SCCIS SCCIS SCCIS SCCIS SCCIS SCCIS
Treatment 5 sessions of PDT 2 sessions of PDT 2 sessions of PDT 2 sessions of PDT 2 sessions of PDT 4 sessions of PDT 2 sessions 2 sessions of PDT 2 sessions of PDT 2 sessions of PDT 2 sessions
and 5-fluorouracil followed by 2 of PDT of PDT
cream cryotherapy followed
sessions by 3
cryotherapy
sessions
Persistence of SCCIS at Yes No No No Yes Yes Yes No No No No
3 months
Clinical findings if Erythematous moist 2 small papulesa Scaly plaque Erythematous Scaly Scaly
persistence detected at patch papules plaque erythematous
3 months or if patcha
recurrence occurred
during follow-up period
RCM done for persistence Yes Yes Yes Yes Yes Yes
or recurrence
FD for persistence and 1+ N/A N/A N/A 1+ 1+
recurrence of SCCIS
Follow-up duration Lost to follow-up 12 months 24 months 24 months 24 months 12 months Lost to 30 months 24 months 18 months 30 months
(months) after 3 months follow-up
after
6 months

a
FD, fluorescence diagnosis, No, number; PDT, photodynamic therapy; RCM, reflectance confocal microscopy; SCCIS, squamous cell carcinoma in situ.
b
Recurrence cases occurred at 7 and 11 months, respectively, for patients 2 and 10.

ª 2019 The International Society of Dermatology

Teoh et al.
Teoh et al. RCM in the diagnosis and monitoring of SCCIS Report 1385

Table 2 RCM findings for newly diagnosed SCCIS prior to sessions of PDT followed by 5-fluorouracil cream 5%. He
skin biopsy declined surgical intervention and subsequently was lost to fol-
low-up.
Patient No (Lesion No) 2 3 (i) 3 (ii) 4 Figures 2a–d show a SCCIS lesion on the chest (patient 7),
which was biopsied prior to undergoing two sessions of PDT
Atypical honeycomb/disarranged epidermal pattern + + + +
and resulted with a persistent nonscaly pink patch which was
Dendritic cells + +
Small bright refractive cells in epidermis + attributed to postinflammatory erythema. RCM imaging showed
Round blood vessels in the superficial dermis + + no residual SCCIS with regular honeycomb configuration of the
Inflammatory cells in dermis + + stratum spinosum and granulosum (Fig. 2f) and FD showed the
absence of fluorescence to confirm complete clearance of
SCCIS (Fig. 2g). There were no signs of clinical recurrence at
2 years post-PDT (Fig. 2e).
Table 3 RCM features for all 11 lesions of which four
SCCIS lesions persisted at 3 months post-PDT, whilst Two patients (patient 2 and 10) who had initial clearance of
patient 2 and 10 demonstrated clinical and confocal findings their SCCIS at 3 months follow-up following two sessions of
consistent with recurrence of SCCIS at 7 and 11 months, PDT subsequently developed clinical recurrence. Patient 2 with
respectively a right elbow SCCIS lesion developed two erythematous
papules at the same site 7 months post-PDT and RCM imaging
Patient No (Lesion no) 1 2 3 (i) 3 (ii) 4 5 6 7 8 9 10 confirmed the presence of atypical keratinocytes with epidermal
disarray and presence of dendritic cells. She declined skin
Atypical honeycomb/ + + + + + +
biopsy or the fluorescence diagnosis. She was treated with topi-
disarranged epidermal
cal imiquimod 5% three times weekly for 6 weeks. A year later,
pattern
Dendritic cells + she showed no clinical or confocal features of SCCIS. Patient
Small bright refractive + 10 who had a lesion on his right fourth toe developed a scaly
cells in epidermis erythematous patch on the previously treated site at 11 months
Round blood vessels + +
post-PDT, of which RCM imaging confirmed the presence of
in the superficial dermis
atypical honeycomb pattern with epidermal disarray. His fluores-
Inflammatory cells in dermis +
cence diagnosis showed fluorescence of 1+, supporting the

Figure 1 (a,b) shows initial clinical presentation of glistening moist erythematous plaque on penis and corresponding fluorescence diagnosis
(2+) confirming the presence of penile SCCIS prior to PDT sessions while (c) shows dysplasia, atypical keratinocytes, and abnormal mitosis
involving the full thickness of the epidermis (hematoxylin and eosin, original magnification 9 100). (d,e) shows less erythematous, smaller
lesion on the penis with reduced FD (1+) after five sessions of PDT. (f,g) depicts the atypical honeycomb pattern and round blood vessels
traversing the dermal papillae, respectively, confirming the presence of SCCIS after five sessions of PDT

ª 2019 The International Society of Dermatology International Journal of Dermatology 2019, 58, 1382–1387
1386 Report RCM in the diagnosis and monitoring of SCCIS Teoh et al.

Figure 2 (a,b) show well-demarcated erythematous scaly plaque on his chest (patient 7) with atypical honeycomb pattern of the spinous-
granular layer with numerous dendritic cells seen on RCM imaging. (c) demonstrates hyperkeratosis and parakeratosis of the stratum
corneum, epidermal thickening, flat rete ridges with atypical keratinocytes involving its full thickness. These atypical cells show random
mitosis, nuclear and cytoplasmic pleomorphism. A dense upper dermal infiltrate of lymphocytes and histiocytes is seen (hematoxylin and
eosin, original magnification 9 100). (d) shows fluorescence 1 + on FD on the lesion. (e,f) show postinflammatory erythema after two
sessions of PDT and RCM imaging demonstrating regular grid-like pattern of the keratinocytes of the spinous-granular layer, respectively.
Flourescence diagnosis also confirmed that there were no residual atypical cells 2 months post-PDT (g)

presence of residual SCCIS. He opted to undergo cryotherapy
at this stage of which he had two sessions at 1 month apart.
His clinical examination and repeat RCM at 30 months showed
no clinical or confocal recurrence.
Discussion
RCM is increasingly used as an adjunctive imaging tool for the
detection of nonmelanoma skin cancer. Our study suggests that
there was good correlation between histological and confocal
features of SCCIS in patients who underwent RCM imaging
prior to biopsy. In addition to clinical and dermoscopy findings,
RCM imaging also has the advantage of identifying the best
location to perform skin biopsies to avoid sampling error. We
found that RCM was useful to monitor for residual SCCIS after
undergoing nonsurgical treatment such as PDT as well as to
detect recurrence of SCCIS. RCM imaging may help to
decrease unnecessary biopsies especially in those who devel-
oped postinflammatory erythema, which may make clinical and
dermoscopic assessment difficult.
Two patients developed recurrence at 7- and 11-month post-
PDT treatment. One of the patients (patient 10) was at high risk
as she had a history of arsenic exposure and had multiple skin
cancers. Studies have shown that SCCIS treated with MAL-
9,10
PDT had a recurrence rate of 29–32% at 24 months.
fore, it should be stressed that all high-risk patients and those
who opted nonsurgical treatment for SCCIS should continue
regular monitoring.
Our RCM findings of SCCIS were consistent with other
studies, demonstrating atypical honeycomb or architectural dis-
array in the stratum granulosum and spinosum as well as
increased blood vessel diameter and number of blood vessels
in some cases.11,12 Atypical honeycomb pattern is defined as
the presence of irregularly shaped keratinocytes with varying
size and often crowding of nuclei in the granular and spinous
layers. The round blood vessels observed in superficial dermis
are due to the dilated blood vessels being located perpendicu-
lar to the RCM plane of imaging.13 Our study also showed
that two out of the eight lesions (four new and four follow-up
cases) had numerous dendritic cells on RCM imaging prior to
their PDT sessions. Dendritic cells in the epidermis could rep-
resent intraepidermal Langerhans cells or melanocytes. As
both cases which demonstrated the dendritic cells were in
nonpigmented lesions and the biopsies of these two lesions
did not show the presence of melanocytes, we postulate that
the dendritic cells were more likely to be Langerhans cells in
origin. Dendritic cells or Langerhans cells are the most potent
antigen-presenting cells and are master regulators of adaptive
immunity because of their potential to elicit tumor-specific
T-cell responses14,15 and play a pivotal role in cancer immune
There- surveillance.16 Various studies have shown that dendritic cells
infiltrate human tumors; however, dendritic cells from certain

International Journal of Dermatology 2019, 58, 1382–1387 ª 2019 The International Society of Dermatology
Teoh et al.
cancers, for example SCC, have been shown to be function-
ally compromised.17 Some studies have demonstrated
decreased ability of DCs in human cancer to stimulate T cells
and induce IFN-c.18 Hence, it has been postulated that dys-
function of DCs, induced by the tumor microenvironment, may
allow tumors to escape immune surveillance.19,19
The limitations of our study include the small sample size
and the lack of histological confirmation in patients who had
persistent residual SCCIS or developed recurrence during their
follow-up. In replacement of histological confirmation, we had a
longer follow-up period of 12–30 months and performed fluores-
cence diagnosis to confirm the presence of SCCIS in patients
who showed clinical or confocal findings suggestive of persis-
tent SCCIS. A positive fluorescence diagnosis is supportive of
recurrence or incomplete clearance of SCCIS and its use has
been validated in other studies.20 It is possible that the positive
fluorescence diagnosis could be due to the presence of actinic
keratosis rather than SCCIS, but as the positive FD was
detected on the same site of prior SCCIS, we treated as a pos-
sible recurrence or persistent SCCIS. Another limitation of our
study is that FD was not available for all patients as some had
declined FD confirmation and preferred to proceed with treat-
ment for their SCCIS lesions if there were clinical suspicion or
confocal findings suggestive of recurrence of SCCIS.
Our study suggests that RCM may be a complementary non-
invasive tool in the diagnosis of SCCIS, although a biopsy is
often necessary to exclude invasive SCC as the depth of RCM
imaging is limited to the level of papillary dermis.
Conclusion
In conclusion, our study suggests that RCM imaging is an
advantageous and practical tool in aiding the diagnosis and
monitoring response of SCCIS to nonsurgical treatment by
avoiding unnecessary biopsies.
References
1 Peterka ES, Lynch FW, Goltz RW. An association between
Bowen’s disease and internal cancer. Arch Dermatol 1961; 84:
623–629.
2 Kao GF. Carcinoma arising in Bowen’s disease. Arch Dermatol
1986; 122: 1124–1126.
3 Cox NH, Eedy DJ, Morton CA. Guidelines for management of
Bowen’s disease. British Association of Dermatologists. Br J
Dermatol 1999; 141: 633–641.
ª 2019 The International Society of Dermatology
RCM in the diagnosis and monitoring of SCCIS Report 1387
4 Sau P, McMarlin SL, Sperling LC, et al. Bowen’s disease of the
nail bed and periungual area. A clinicopathologic analysis of
seven cases. Arch Dermatol 1994; 130: 204–209.
5 Perruchoud DL, Varonier C, Haneke E, et al. Bowen disease of
the nail unit: a retrospective study of 12 cases and their
association with human papillomaviruses. J Eur Acad Dermatol
Venereol 2016; 30: 1503–1506.
6 Guo HR, Yu HS, Hu H, et al. Arsenic in drinking water and skin
cancers: cell-type specificity (Taiwan, ROC). Cancer Causes
Control 2001;12:909–916.
7 de Leeuw J, van der Beek N, Neugebauer WD, et al.
Fluorescence detection and diagnosis of non-melanoma skin
cancer at an early stage. Lasers Surg Med 2009; 41: 96–103.
8 Kleinpenning MM, Wolberink EW, Smits T, et al. Fluorescence
diagnosis in actinic keratosis and squamous cell carcinoma.
Photodermatol Photoimmunol Photomed 2010; 26: 297–302.
9 Calzavara-Pinton PG, Venturini M, Sala R, et al.
Methylaminolaevulinate-based photodynamic therapy of
Bowen’s disease and squamous cell carcinoma. Br J Dermatol
2008; 159: 137–144.
10 Lehmann P. Methyl aminolaevulinate-photodynamic therapy: a
review of clinical trials in the treatment of actinic keratoses and
nonmelanoma skin cancer. Br J Dermatol 2007; 156: 793–801.
11 Rishpon A, Kim N, Scope A, et al. Reflectance confocal
microscopy criteria for squamous cell carcinomas and actinic
keratoses. Arch Dermatol 2009; 145: 766–772.
12 Peppelman M, Nguyen KP, Hoogedorn L, et al. Reflectance
confocal microscopy: non-invasive distinction between actinic
keratosis and squamous cell carcinoma. J Eur Acad Dermatol
Venereol 2015; 29: 1302–1309.
13 Shahriari N, Grant-Kels JM, Rabinovitz H, et al. In vivo
reflectance confocal microscopy image interpretation for the
dermatopathologist. J Cutan Pathol 2018; 45: 187–197.
14 Steinman RM, Banchereau J. Taking dendritic cells into
medicine. Nature 2007; 449: 419–426.
15 Fricke I, Gabrilovich DI. Dendritic cells and tumor
microenvironment: a dangerous liaison. Immunol Invest 2006;
35: 459–483.
16 Gottfried E, Kreutz M, Mackensen A. Tumor-induced modulation
of dendritic cell function. Cytokine Growth Factor Rev 2008; 19:
65–77.
17 Chaput N, Conforti R, Viaud S, et al. The Janus face of
dendritic cells in cancer. Oncogene 2008; 27: 5920–5931.
18 Perrot I, Blanchard D, Freymond N, et al. Dendritic cells
infiltrating human non-small cell lung cancer are blocked at
immature stage. J Immunol 2007; 178: 2763–2769.
19 Pinzon-Charry A, Maxwell T, Lopez JA. Dendritic cell
dysfunction in cancer: a mechanism for immunosuppression.
Immunol Cell Biol 2005; 83: 451–461.
20 Truchuelo MT, Pe rez B, Ferna ndez-Guarino M, et al. Fluorescence
diagnosis and photodynamic therapy for Bowen’s disease
treatment. J Eur Acad Dermatol Venereol 2014; 28: 86–93.
International Journal of Dermatology 2019, 58, 1382–1387