Line-field confocal optical coherence tomography in dermato-oncology: A literature review towards harmonized histopathology-integrated terminology.

Non-invasive diagnostics like line-field confocal optical coherence tomography (LC-OCT) are being implemented in dermato-oncology. However, unification of terminology in LC-OCT is lacking. By reviewing the LC-OCT literature in the field of dermato-oncology, this study aimed to develop a unified terminological glossary integrated with traditional histopathology. A PRISMA-guided literature-search was conducted for English-language publications on LC-OCT of actinic keratosis (AK), keratinocyte carcinoma (KC), and malignant melanoma (MM). Study characteristics and terminology were compiled. To harmonize LC-OCT terminology and integrate with histopathology, synonymous terms for image features of AK, KC, and MM were merged by two authors, organized by skin layer and lesion-type. A subset of key LC-OCT image-markers with histopathological correlates that in combination were typical of AK, squamous cell carcinoma in situ (SCCis), invasive squamous cell carcinoma (SCC), basal cell carcinoma (BCC), and MM in traditional histopathology, were selected from the glossary by an experienced dermatopathologist. Seventeen observational studies of AK (7 studies), KC (13 studies), MM (7 studies) utilizing LC-OCT were included, with 117 terms describing either AK, KC, or MM. These were merged to produce 45 merged-terms (61.5% reduction); 5 assigned to the stratum corneum (SC), 23 to the viable epidermis, 2 to dermo-epidermal junction (DEJ) and 15 to the dermis. For each lesion, mandatory key image-markers were a well-defined DEJ and presence of mild/moderate but not severe epidermal dysplasia for AK, severe epidermal dysplasia and well-defined DEJ for SCCis, interrupted DEJ and/or dermal broad infiltrative strands for invasive SCC, dermal lobules connected and/or unconnected to the epidermis for BCC, as well as single atypical melanocytes and/or nest of atypical melanocytes in the epidermis or dermis for MM. This review compiles evidence on LC-OCT in dermato-oncology, providing a harmonized histopathology-integrated terminology and key image-markers for each lesion. Further evaluation is required to determine the clinical value of these findings.

Characterizing the cutaneous late effects of allogeneic hematopoietic stem cell transplantation: A systematic review.

BACKGROUND: There is a well-documented risk of secondary cutaneous malignancies following allogeneic hematopoietic stem cell transplant (HSCT), but data on risk in pediatric populations are limited. The objective of this study is to perform a systematic review of reported features and outcomes of skin cancers in pediatric allogeneic HSCT recipients. METHODS: MEDLINE, EMBASE, CINAHL, Cochrane, and Web of Science were systematically searched (Prospero CRD42022342139). Studies reporting cutaneous cancer outcomes were included if the age at transplant was ≤19 years. Titles, abstracts, and full-text articles were screened in duplicate. RESULTS: Out of 824 citations that were screened, 12 articles were selected for analysis. The final sample included 67 pediatric HSCT recipients, comprising 65 allogeneic transplant recipients and 2 cases of HSCT with an unknown donor type. The median age at transplant and skin cancer diagnosis were 7.4 and 13 years, respectively. Out of the 67 pediatric HSCT recipients, some patients developed more than one lesion, resulting in 71 lesions. The most common skin cancer type was cutaneous squamous cell carcinoma (32 lesions), followed by basal cell carcinoma (25 lesions). The median latency period between HSCT and skin cancer diagnosis ranged from 0 to 29 years. Identified risk factors for skin cancers included younger age at the time of transplant, exposure to total body irradiation, prolonged post-transplant immunosuppression, graft versus host disease, and sunburn. CONCLUSION: Skin cancers are reported in pediatric allogeneic HSCT recipients, and the risk appears to be increased. More data are needed to better characterize this risk.

[Advances in optical coherence tomography]. / Neues von der optischen Kohärenztomographie.

Optical coherence tomography (OCT) has been able to establish itself in recent years not only in academic-scientific, but also in everyday dermatological practice. Its focus lies on epithelial tumors of the skin, which can be diagnosed intuitively and within a few seconds. Thus, basal cell carcinomas, actinic keratoses, and different stages of field cancerization can be diagnosed and monitored for response to therapy or possible recurrence. This often helps to avoid invasive sample extraction. Recently, the field of OCT and its latest advancement, dynamic OCT (D-OCT), has been expanded to include non-oncologic dermatological diseases. This encompasses inflammatory dermatoses and the analysis of physiological skin parameters such as hydration. Thanks to automated vascular imaging and the measurement of objective parameters such as epidermal thickness, blood flow at depth, optical attenuation coefficient, and skin roughness, more and more characteristics of the skin can be studied in a noninvasive and standardized way. New potential areas of application are eczema, contact allergic dermatitis, psoriasis, rosacea, telangiectasia, acute and chronic wounds, melasma and nevus flammeus but also melanocytic lesions.

[Ex vivo confocal laser scanning microscopy for melanocytic lesions and autoimmune diseases]. / Ex-vivo konfokale Laserscanmikroskopie bei melanozytären Läsionen und Autoimmunerkrankungen.

BACKGROUND: Ex vivo confocal laser scanning microscopy (CLSM) enables bedside histology and offers the surgeon a direct intraoperative tissue examination. OBJECTIVES: To determine whether this innovative, ultra-fast diagnostic tool can be expanded beyond nonmelanoma skin cancer, particularly basal cell carcinoma, to other indications including melanocytic lesions and autoimmune diseases. MATERIALS AND METHODS: Review of literature and summary of the current knowledge and experience of the use of ex vivo CLSM in melanocytic lesions and in autoimmune diseases. RESULTS: Up to date experience of the use of ex vivo CLSM in melanocytic lesions and in autoimmune diseases is limited but promising. Current knowledge on melanocytic lesions in ex vivo CLSM and their examples together with classic ex vivo CLSM features are presented. Previous results on the use of ex vivo CLSM in autoimmune dermatoses are presented, and future application possibilities of ex vivo CLSM are discussed. CONCLUSIONS: The method is particularly suitable for the rapid examination of basal cell carcinomas during Mohs surgery but could also be used in the future for the intraoperative examination of melanocytic and autoimmune skin lesions.

[Comparison of the clinicopathological features between adenoid basal cell carcinoma and adenoid cystic carcinoma of the cervix].

Objective: To compare the clinical and histopathological characteristics of cervical adenoid basal cell carcinoma and adenoid cystic carcinoma for improving the diagnosis accuracy and differential diagnosis of these tumors. Methods: A retrospective study was conducted on 9 cases of cervical adenoid basal cell carcinoma and 3 cases of adenoid cystic carcinoma which were diagnosed and consulted at the First Medical Center of PLA General Hospital from March 2009 to April 2019. Detailed clinical data were reviewed. All pathological sections and immunohistochemical results were reviewed and the clinicopathological characteristics were analyzed. Follow-up information by telephone was collected and relevant literature was consulted. Results: Both tumors were more commonly found in postmenopausal women (the age of onset ranged 43-74 years). Adenoid basal cell carcinoma was often clinical asymptomatic. Most of them presented as abnormal smears of the cervix during physical examination, and there was no definite mass in colposcopy.Adenoid cystic carcinoma was mostly presented with abnormal vaginal bleeding. A mass was seen in colposcopy.Histologically, the two tumors were characterized by nest-like growth of the tumors, consisting of basal-like tumor cells, and often surrounded by palisade structures. The two lesions might coexist, or be mixed with squamous cell carcinoma or high-grade squamous intraepithelial lesions. The difference was that adenoid basal cell carcinoma was mostly located at the junction of cervical squamous epithelium and columnar epithelium and beneath the overlying epithelium, the tumor cells were arranged in nests, with squamous differentiation in the center of the nests, or in double-layer adenoid arrangement. The cell morphology was bland with occasional mitoses, and the stromal reaction was not obvious. And adenoid cystic carcinoma cells in the nest arranged like a sieve, the homogenous red-stained and blue-stained secretions were observed in the sieve holes, with obvious cell atypia, frequent mitoses, and obvious stromal reaction.In one case of adenoid cystic carcinoma, sarcomatoid area presented around the nests.Both of them were positive in clinical HPV test. Among the 9 cases of adenoid basal cell carcinoma, 3 were tested for HPV and 5 were tested for p16, and all showed positive expression. Among the 3 cases of adenoid cystic carcinoma, 2 were tested for HPV and 3 were tested for p16, both of which showed positive expression. Telephone follow-up was conducted by June 2019(follow-up time ranged 2-37 months). No recurrence or metastasis occurred in 7 of the 9 cases of adenoid basal cell carcinoma, while 1 case had a ground-glass nodule in lung and another had recurrence of vaginal stump 32 months after the surgery.One case of adenoid cystic carcinoma developed lung metastasis 8 months after surgery and died 2 years after surgery; another case was followed up for 6 months, which showed no recurrence or metastasis; the third case was lost to follow-up. Conclusions: Both adenoid cystic carcinoma and adenoid basal cell carcinoma of the cervix are the tumors originating from cervical reserve cells and are associated with high-risk HPV infection. Due to the differences in clinical treatment and prognosis, careful histological evaluation and immunohistochemical analysis should be carried out to make accurate pathological diagnosis.

[What's new in oncodermatology in 2015?]. / Quoi de neuf en oncodermatologie en 2015?

Oncodermatology is the topic of constant innovation since 5 years. These innovations have drammatically modified the prognostic of skin cancers and induced a change in the paradigm that drives the whole oncology. Once again in 2015, melanoma is the key topic of scientific communication, with promising results. However, unmet clinical needs must be kept in light. Some diseases, such as squamous cell carcinoma or cutaneous lymphoma remain poorly evaluated. This article was designed as a review of litterature. All keywords of oncodermatology were searched in the main journals of dermatology, oncology and internal medicine. Despite methodologic restrictions, the number of articles imposed a choice based on opinion. The final goal was to transmit author's enthousiasm and the most important results.

Long-term follow-up of patients with high-risk facial basal cell carcinoma treated with interferon.

BACKGROUND: Surgery is the treatment of choice for patients with basal cell carcinoma (BCC). When surgery is not a choice, only radiotherapy is recommended for patients with high-risk facial BCC. Interferon could be an acceptable therapeutic option for these patients. OBJECTIVE: To evaluate the long-term clinical response to interferon therapy in patients with high-risk facial BCC. METHODS: Patients with high-risk facial BCC were treated with perilesional injections of alpha-2b+ gamma interferons. Those with incomplete clinical response were reevaluated, their residual tumors excised, and declared cured. Patients treated with interferon and those treated with interferon plus surgery were followed for five years. Time to recurrence and the emergence of a new facial BCC were estimated by Kaplan-Meier survival analysis. Adverse events were documented. RESULTS: This study included 195 participants; 143 (73.3%) showed a complete response (95% CI 67.2‒80.1). Patients developed recurrence after a mean of 55 months (95% CI 53.8‒57.4). The estimated rate of recurrence was 12.3% (95% CI 7.4‒17.1). Patients developed a new BCC after a mean of 52.7 months (95% CI 50.4‒54.9). The estimated rate for development of a new BCC was 20.0% (95% CI 14.4‒25.9). Fifteen (7.7%) patients abandoned the study during follow-up. Adverse events were frequent but moderate or mild; fever and local pain were the most frequent. STUDY LIMITATIONS: Observational cohort design without a control group for comparison. CONCLUSIONS: Perilesional injections of alpha-2b+ gamma interferons in patients with facial high-risk BCC offer a satisfactory cure rate after five years of follow-up with an acceptable safety profile.

Eyelid tumours and pseudotumours in Hong Kong: a ten-year experience.

OBJECTIVE: To describe the clinicopathological characteristics of patients with eyelid tumours in Hong Kong. DESIGN: Retrospective case series. SETTING: A tertiary eye centre in Hong Kong. PATIENTS: A computerised retrieval system was used to identify all patients who underwent eyelid mass excisions with histological reports, encountered in the period 2000 to 2009, in a tertiary eye centre. The demographics (age, gender), clinical features (laterality, tumour topography), and the pathological diagnosis of each patient were documented. Descriptive statistical tabulation and analyses were performed on the data. RESULTS: In all, 198 patients were identified; all were Chinese. Their mean age was 54 years for benign lesions and 68 years for malignant ones. Women were more commonly affected. Benign tumourous lesions occurred more commonly on the upper (n=91; 54%) than lower eyelid (n=79; 47%), whereas malignant lesions more often affected the lower (n=17, 61%) than upper (n=11, 39%) eyelid. The distribution of left and right eye involvement was similar (103 vs 101, respectively). In six patients, there were bilateral benign lesion. Regarding benign masses, 45 (27%) were intradermal neavi, 38 (22%) were squamous papillomas, 25 (15%) were seborrhoeic keratosis lesions, 14 (8%) were epidermoid cysts, and 7 (4%) were compound naevi. Regarding malignant eyelid tumours, the most common was basal cell carcinomas (n=12, 43%), 5 (18%) were squamous cell carcinomas, 3 (11%) were actinic keratosis lesions, and 2 (7%) each were sebaceous gland carcinomas and melanomas. CONCLUSION: Benign lesions constituted the majority of these eyelid tumours. Among the malignant lesions, basal cell carcinoma was the commonest type, with lower lid involvement in majority. Sebaceous gland carcinoma is not rare, which is in contrast to Caucasian populations. The relative frequencies of the most common malignant tumours in Hong Kong differed substantially from those reported in other Asian studies.

Chemotherapeutical treatment of basal cell carcinoma with bleomycin via microinfusion of the drug into the skin (MMP®).

BACKGROUND: Bleomycin is a chemotherapeutical drug used to treat several neoplasias, including non-melanoma skin cancer; it is effective in the treatment of basal cell carcinoma (BCC) via intralesional infiltration. Transdermal drug delivery, which includes technologies such as CO2 Laser, Dermapen, Dermaroller and MMP®, delivers the desired medication to treat skin neoplasias and also acts in skin rejuvenation. OBJECTIVE: To treat BCC lesions using bleomycin via MMP®. METHODS: Ninety-eight BCC lesions in different anatomical areas were treated using MMP® technology to administer and uniformly distribute bleomycin throughout the lesion and in the established safety margin. RESULTS: The cure rate after six months was 96.94%; and recurrences were not associated with lesion size and/or depth. Adverse effects were the expected ones. STUDY LIMITATIONS: The follow-up time was only six months. CONCLUSION: This therapeutic route showed to be promising and effective.

Dermoscopy of very small basal cell carcinoma (≤3mm).

BACKGROUND: Basal cell carcinoma (BCC) dermoscopy is key to lower the biopsy threshold of suspicious lesions. There is a scarcity of published data on the dermoscopy of very small BCC (≤3mm) and its differences from larger BCCs. OBJECTIVE: To describe and compare dermoscopic features of BCCs measuring ≤3mm, with those from 3 to 10mm. METHODS: An analytical cross-sectional study, included biopsy-proven BCCs that had dermoscopic photographic images, between January 2017 and December 2022 in a Skin Cancer Center in Medellín, Colombia. Demographic, clinic-pathological and dermoscopic features were compared between very small BCCs (vsBCCs) and a reference group. RESULTS: A total of 326 BCCs in 196 patients were included, of whom 60% were male. The most common Fitzpatrick phototype was III. vsBCCs accounted for 25% of the lesions (81/326). Face and neck were the most frequent locations (53%), especially in very small tumors. The nodular type was more common in very small tumors than in larger lesions, the superficial type was less frequent, and aggressive types were equally prevalent in both groups. On dermoscopy, very small tumors were statistically more likely to present pigmented structures than reference lesions, especially blue-gray dots (67% vs. 54%), vessels were less frequent, particularly short-fine telangiectasias (SFT) (52% vs. 66%), as were other structures such as shiny white structures (SWS), ulceration, micro-erosions, and scales. STUDY LIMITATIONS: Latin-American sample, lacks information on dark phototypes CONCLUSIONS: Pigmented structures, especially blue-gray dots, were most common in vsBCCs when compared to larger lesions; SFT, SWS and other findings were less prevalent.

Immune microenvironment of basal cell carcinoma and tumor regression following combined PD-1/LAG-3 blockade.

Systemic treatment options for patients with locally advanced or metastatic basal cell carcinoma (BCC) are limited, particularly when tumors are refractory to anti-programmed cell death protein-1 (PD-1). A better understanding of immune checkpoint expression within the BCC tumor microenvironment may inform combinatorial treatment strategies to optimize response rates. CD3, PD-1, programmed death ligand-1 (PD-L1), lymphocyte activation gene 3 (LAG-3), and T-cell immunoglobulin domain and mucin domain 3 (TIM-3)+ cell densities within the tumor microenvironment of 34 archival, histologically aggressive BCCs were assessed. Tumor infiltrating lymphocyte (TIL) expression of PD-1, PD-L1, and LAG-3, and to a lesser degree TIM-3, correlated with increasing CD3+ T-cell densities (Pearson's r=0.89, 0.72, 0.87, and 0.63, respectively). 100% of BCCs (34/34) demonstrated LAG-3 and PD-1 expression in >1% TIL; and the correlation between PD-1 and LAG-3 densities was high (Pearson's r=0.89). LAG-3 was expressed at ~50% of the level of PD-1. Additionally, we present a patient with locally-advanced BCC who experienced stable disease during and after 45 weeks of first-line anti-PD-1 (nivolumab), followed by a partial response after the addition of anti-LAG-3 (relatlimab). Longitudinal biopsies throughout the treatment course showed a graduated increase in LAG-3 expression after anti-PD-1 therapy, lending support for coordinated immunosuppression and suggesting LAG-3 as a co-target for combination therapy to augment the clinical impact of anti-PD-(L)1.

Histopathological Pattern of Head and Neck Recurrent BCC After Previous Cryotherapy.

Surgical resection is the gold standard treatment for basal cell carcinomas, although there is literature supporting cryotherapy for low-risk cases. Our aim was to compare the histopathological aspects of recurrent postcryotherapy head and neck cutaneous BCC with de novo tumors, using a case-control study. 51 Recurrent postcryotherapy cases were selected between January 2017 and December 2021 and compared to 132 controls filtered from a consecutive series of de novo head and neck cutaneous BCC operated between January and December 2021. Aggressive variants, multifocality, invasion beyond adipose tissue and higher Clark levels were associated with recurrent cases on multivariate analysis. Previous cryotherapy treatment may have contributed to an increased risk of more aggressive recurrent disease and caution using this treatment modality is advised. Supplementary Information: The online version contains supplementary material available at 10.1007/s12070-023-03919-7.