Subtypes Of Basal Cell Carcinoma Research Articles

High Frequency Ultrasound of Basal Cell Carcinomas: Ultrasonographic Features and Histological Subtypes, a Retrospective Study of 100 Tumors.

(1) Background: 22 MHz high frequency ultrasound (HFUS) is a non-invasive imaging technique that gives information on depth, length, volume and shape of skin tumors. (2) Methods: We reviewed the clinical, ultrasound, and histological records of 54 patients with 100 histologically confirmed basal cell carcinoma (BCC) tumors with the use of HFUS. (3) Results: Most infiltrative tumors (n = 16/21, 76.2%) were irregular shaped, followed by five (23.8%) being round shaped; most superficial tumors (n = 25/29, 86.2%) were ribbon shaped, followed by four (13.8%) being round shaped; most nodular tumors (n = 26/33, 78.8%) were round shaped, followed by seven (21.2%) that were irregular shaped; and, lastly, all microdular tumors (n = 2/2, 100%) were round shaped. Strong evidence of association (p = 0.000) was observed between the histological subtype and tumor shape as seen using the HFUS. No evidence of association was found between the histological subtype and tumor margin (p > 0.005). Cohen's Kappa statistic to assess the agreement between BCC subtypes evaluated by histological examination and U/S appearance was calculated equal to 0.8251 (almost perfect agreement). (4) Conclusions: HFUS appears to be a reliable technique for the pre-operative evaluation of BCCs, assisting physicians to decide on the optimal therapeutic approach.

Clinicopathological Factors Influencing Resection Margin Involvement During Mohs Micrographic Surgery for Skin Tumors.

Mohs micrographic surgery (MMS) is a specialized procedure for removing skin tumors. Intraoperative assessment of the resection margin (RM) status using frozen section examination is a crucial component of MMS. This study aimed to identify significant clinicopathological characteristics that could help surgeons determine the optimal surgical extent. One hundred and fifty-one patients with primary skin tumors were included. The relationship between RM involvement and the clinico-pathological characteristics was analyzed for each histological type. Basal cell carcinoma (BCC) was significantly more likely to exhibit positive RMs and required additional excision during MMS compared to squamous cell carcinoma. In addition, the probability of RM involvement was significantly higher in high-risk BCC subtypes. When planning MMS, considering the histological type and presence of high-risk morphology may help surgeons perform more effective procedures.

Single-Cell Profiling Reveals Sustained Immune Infiltration, Surveillance, and Tumor Heterogeneity in Infiltrative Basal Cell Carcinoma

Infiltrative basal cell carcinoma (iBCC) is a particularly aggressive subtype of basal cell carcinoma that tends to progress and recur after surgery, and its malignancy is closely related to the tumor microenvironment. In this study, we performed a comprehensive single-cell RNA analysis to profile 29,334 cells from iBCC and adjacent normal skin. We found active immune collaborations enriched in iBCC. Specifically, SPP1+CXCL9/10high macrophage 1 had strong BAFF signaling with plasma cells, and T follicular helper-like cells highly expressed the B-cell chemokine CXCL13. Heterogeneous proinflammatory SPP1+CXCL9/10high macrophage 1 and angiogenesis-related SPP1+CCL2high macrophage 1 were identified within the tumor microenvironment. Interestingly, we found an upregulation of major histocompatibility complex I molecules in fibroblasts in iBCC compared with those in adjacent normal skin. Moreover, MDK signals derived from malignant basal cells were markedly increased, and their expression was an independent factor in predicting the infiltration depth of iBCC, emphasizing its role in driving malignancy and remodeling the tumor microenvironment. In addition, we identified differentiation-associated SOSTDC1+IGFBP5+CTSV+ malignant basal subtype 1 and epithelial-mesenchymal transition-associated TNC+SFRP1+CHGA+ malignant basal subtype 2 cells. The high expression of malignant basal 2 cell markers was associated with the invasion and recurrence of iBCC. Altogether, our study helps to elucidate the cellular heterogeneity in iBCC and provides potential therapeutic targets for clinical research.

Recurrence or de novo? Intradermal Basal Cell Carcinoma of the Scrotum: A Report of Two Cases

Basal cell carcinoma (BCC) is the most common cutaneous malignancy, usually occurring in sun-exposed areas. Although BCC in the scrotal region is uncommon, it carries a higher risk of metastasis than BCC at other sites. Here, we report two cases of BCC that developed in the scrotal region: Case 1 presented as a superficial nodule and Case 2 as a subcutaneous nodule. Histopathologically, both tumors lacked continuity with the surface epidermis and formed an intradermal nodule. In Case 1, BCC occurred for the first time and presumably developed de novo. Case 2 underwent excision of a scrotal BCC 5 years previously, and the histopathological diagnosis at that time was nodular BCC. However, when the original specimen was re-examined, it was determined that, although the tumor had been completely resected, part of the lesion had moved away from the nodular area to represent a micronodular phenotype, an aggressive BCC subtype. We hypothesized that partial evolution from a nodular to a micronodular phenotype may have contributed to the recurrence of BCC in Case 2.

Non-invasive imaging techniques in presurgical margin assessment of basal cell carcinoma: Current evidence.

The diagnosis of basal cell carcinoma (BCC) is based on clinical and dermoscopical features. In uncertain cases, innovative imaging techniques, such as reflectance confocal microscopy (RCM) and optical coherence tomography (OCT), have been used. The main limitation of these techniques is the inability to study deep margins. HFUS (high-frequency ultrasound) and the most recent UHFUS (ultra-high-frequency ultrasound) have been used in various applications in dermatology, but they are not yet routinely used in the diagnosis of BCC. A key point in clinical practice is to find an imaging technique that can help to reduce post-surgical recurrences with a careful presurgical assessment of the lesional margins. This technique should show high sensitivity, specificity, reproducibility and simplicity of execution. This concept is very important for the optimal management of patients who are often elderly and have many comorbidities. The aim of the paper is to analyse the characteristics of current imaging techniques and the studies in the literature on this topic. The authors independently searched the MEDLINE, PubMed, Embase, Scopus, ScienceDirect and Cochrane Library databases for studies looking for non-invasive imaging techniques for the presurgical margin assessment of BCC. Preoperative study of the BCC subtype can help to obtain a complete excision with free margins. Different non-invasive imaging techniques have been studied for in vivo evaluation of tumour margins, comparing the histologic evaluation with a radical surgery. The possibility to study the lateral and deep margins would allow a reduction of recurrences and sparing of healthy tissue. HFUS and UHFUS represent the most promising, non-invasive techniques for the pre-operative study of BCC facilitating the characterization of vascularization, deep lateral margins and high-risk subtypes, although they are limited by insufficient literature unlike RCM and OCT.

Clinical, Dermoscopic and Histopathological Evaluation of Basal Cell Carcinoma.

Dermoscopy aids in identifying histopathological subtypes and the presence of clinically undetectable pigmentation in basal cell carcinoma (BCC). To investigate the dermoscopic features of BCC subtypes and better understand non-classical dermoscopic patterns. Clinical and histopathological findings were recorded by a dermatologist who was blinded to the dermoscopic images. Dermoscopic images were interpreted by two independent dermatologists blinded to the patients' clinical and histopathologic diagnosis. Agreement between the two evaluators and with histopathological findings was evaluated using Cohen's kappa coefficient analysis. The study included a total of 96 BBC patients with 6 histopathologic variants: nodular (n=48, 50%), infiltrative (n=14, 14.6%), mixed (n=11, 11.5%), superficial (n=10, 10.4%), basosquamous (n=10, 10.4%), and micronodular (n=3, 3.1%). Clinical and dermoscopic diagnosis of pigmented BCC showed high agreement with histopathological diagnosis. The most common dermoscopic findings according to subtype were as follows: nodular BCC: shiny white-red structureless background (85.4%), white structureless areas (75%), and arborizing vessels (70.7%); infiltrative BCC: shiny white-red structureless background (92.9%), white structureless areas (78.6%), arborizing vessels (71.4%); mixed BCC: shiny white-red structureless background (72.7%), white structureless areas (54.4%), and short fine telangiectasias (54.4%); superficial BCC: shiny white-red structureless background (100%), short fine telangiectasias (70%); basosquamous BCC: shiny white-red structureless background (100%), white structureless areas (80%), keratin masses (80%); micronodular BCC: short fine telangiectasias (100%). In this study, arborizing vessels were the most common classical dermoscopic feature of BCC, while shiny white-red structureless background and white structureless areas were the most frequent non-classical dermoscopic features.

Myofibroblast stroma differentiation in infiltrative basal cell carcinoma is accompanied by regulatory T-cells.

The implications of infiltrative compared to non-infiltrative growth of cutaneous basal cell carcinoma (BCC) on the tumor stroma and immune cell landscape are unknown. This is of clinical importance, because infiltrative BCCs, in contrast to other BCC subtypes, are more likely to relapse after surgery and radiotherapy. This descriptive cross-sectional study analyzed 38 BCCs collected from 2018 to 2021. In the first cohort (n=28), immune cells were characterized by immunohistochemistry and multiplex immunofluorescence staining for CD3, CD8, CD68, Foxp3, and α-SMA protein expression. In the second cohort (n=10) with matched characteristics (age, sex, location, and BCC subtype), inflammatory parameters, including TGF-β1, TGF-β2, ACTA2, IL-10, IL-12A, and Foxp3, were quantified via RT-qPCR after isolating mRNA from BCC tissue samples and perilesional skin. Infiltrative BCCs showed significantly increased levels of α-SMA expression in fibroblasts (p=0.0001) and higher levels of Foxp3+ (p=0.0023) and CD3+ (p=0.0443) T-cells compared to non-infiltrative BCCs. CD3+ (p=0.0171) and regulatory T-cells (p=0.0026) were significantly increased in α-SMA-positive tumor stroma, whereas CD8+ T-cells (p=0.1329) and CD68+ myeloid cells (p=0.2337) were not affected. TGF-β1 and TGF-β2 correlated significantly with ACTA2/α-SMA mRNA expression (p=0.020, p=0.005). Infiltrative growth of BCCs shows a myofibroblastic stroma differentiation and is accompanied by an immunosuppressive tumor microenvironment.

Growth rate of basal cell carcinoma: a meta-analysis and systematic review.

Basal cell carcinoma (BCC) is the most common skin cancer, especially in fair-skinned adults, and the lifetime risk of its incidence in this population is estimated to be approximately 30%. We present a meta-analysis and systematic review summarizing the size of the growth rate in BCC, depending also on its subtypes. To find all relevant studies, online medical databases such as PubMed, Scopus, Embase, Web of Science, and Google Scholar were searched regarding the growth rate of BCC. A total of 7 studies were included in this review. Five studies contained data on the growth rate of basal cell carcinomas. The mean growth rate for the longer axis of the BCC was established to be 0.71 mm/month (standard error: 0.22). The presented analysis shows that BCC is generally a slow-growing tumour, with a mean growth rate of about 0.7 mm/month. However, it was proven that this growth rate differs depending on the BCC subtype.

Expression of Connexin 32 and Connexin 43 gap junction proteins in basal and squamous cell carcinomas

Gap junctions play a role in intercellular communication in the epithelium, muscle and nerve tissues, and many more tissues and organs. These linking regions and the proteins forming them are called connexins (Cx). Recent studies show that cellular homeostatic equilibrium can be influenced by connexins. In this study, the expression of Cx43 and Cx32 in basal cell carcinoma (BCC) and squamous cell carcinomas (SCC) is tried studied. A total of 45 cases, 23 male and 22 female, were included in the study. Twenty of the cases were SCC and twenty-five were BCC. Retrospective data from records were examined and specimens were investigated by immunohistochemistry staining. It was determined that the results of Cx 43 and Cx 32 staining changed according to the tumor type of cases (P = 0,020). It was determined that the results of Cx43 and Cx32 staining did not change according to the sex and age, BCC and SCC subtype, and location. Losses of Cx43 and Cx32 have been shown to be associated with tumor types. We believe that it can be used as a support marker of SCC and BCC differential diagnosis.

Expression of BerEP4 and CD10 IHC Markers in Basal Cell Carcinoma, Squamous Cell Carcinoma and Adnexal Tumours of Follicular Differentiation: A Comparative Study.

Basal cell carcinoma (BCC) is the most common cutaneous malignancy. In most cases, BCC can be diagnosed by its characteristic histopathological features. The differential diagnosis includes basaloid squamous cell carcinoma (SqCC) and adnexal tumours of follicular differentiation. Cluster of differentiation 10 (CD10) and name of an immunostain (BerEP4) are reported to be useful in differentiating between them. The primary objective was to compare the expression of BerEP4 and CD10 in BCC with that of SqCC and adnexal tumours of follicular differentiation, and the secondary objective was to evaluate the proportion of different histological subtypes of BCC. Twenty-eight cases of BCCs, 34 cases of SqCCs and 16 adnexal tumours of follicular differentiation received in the institution during the study period January 2017 to June 2018 were included in this descriptive study. Immunostaining with CD10 and BerEP4 was performed, and the staining pattern was studied in all 78 cases. A detailed histopathological evaluation including subtyping was carried out for BCC cases. All BCCs showed positivity with CD10 and BerEP4, but the intensity and pattern varied. Squamous cell carcinomas were completely negative for BerEP4 and CD10 in tumour cells, and 25 of 34 cases showed stromal CD10 positivity. Among adnexal tumours of follicular differentiation, proliferating trichilemmal tumour was completely negative for both markers; other adnexal tumours (n = 11/16) showed peritumoral stromal accentuation for CD10, and nine of 11 cases showed BerEP4 tumour cell positivity (P < 0.001). BerEP4 can reliably detect BCCs of all types and distinguish between BCC and SqCC, but it is unable to do so for adnexal tumours such as trichoepithelioma, trichilemmoma and trichoblastoma. CD10 is a useful adjunct marker in distinguishing both trichoepithelioma (TE) and SqCC from BCC. CD10-positive tumour cells favour a diagnosis of BCC and peritumoral stromal accentuation for trichoblastoma (TB) and trichilemmoma (TL). Tumour cells in SqCC are almost always negative for CD10. A combined immunohistochemistry (IHC) panel of CD10 and BerEP4 can serve as a very reliable adjunctive in the diagnosis of BCC.

Expression of Ki-67 antigen in various histological types of BASAL CELL CARCINOMA

Background : Basal cell carcinoma (BCC) is the most commonest malignant tumor of the skin especially fair-skinned individuals makes up roughly 70–80% of all malignant tumors. In certainty, this malignancy had a variety of many tumor sub-types, through a distinct histo-morphological appearance and biological function. Unlike other tumors, usually has an affirmative clinical course, developing slowly and just locally. Antibodies against “Ki-67 antigen” or proliferating Cell nuclear antigen (PCNA) are typically used in immunohistochemistry to detect the proliferative activity (growth fraction) of malignancies. Aim of the study : This study aims to examine the tumor cells' proliferative status utilizing an immunohistochemistry analysis of the “Ki-67” antigen in skin biopsy specimens of different sub-type of BCCs. Material and methods : A Case series study enrolling 35 biopsies sampled from retrospectively selected cases of cutaneous BCCs were registered in the research. Results : Thirty five biopsy (31 Primary, 4 Recurrent)of different histological types from 35 patients (11 male, 24 female) were included. The patient’s age ranged from 36 to 75 years (with mean of 59.2 year) .In this study results showed that commonest site of involvement was the face in 71.4% of cases , and there was significant association between tumor size and the Ki67 level and grade, the study reported a non-significant association between the tumor histological subtype and Ki67 level. Discussion : The data showed that there were a wide range of ki67 level (2 to 70%) among various histological growth subtype of basal cell carcinoma, higher proliferative index indicate more malignant potential and lower proliferative index mean less aggressive tumor. So the wide range of proliferation which had been reported in the BCC illuminate the wide spectrum of biological activity of tumor.

Quantitative collagen analysis using second harmonic generation images for the detection of basal cell carcinoma with ex vivo multiphoton microscopy.

Basal cell carcinoma (BCC) is the most common skin cancer, and its incidence is rising. Millions of benign biopsies are performed annually for BCC diagnosis, increasing morbidity, and healthcare costs. Non-invasive in vivo technologies such as multiphoton microscopy (MPM) can aid in diagnosing BCC, reducing the need for biopsies. Furthermore, the second harmonic generation (SHG) signal generated from MPM can classify and prognosticate cancers based on extracellular matrix changes, especially collagen type I. We explored the potential of MPM to differentiate collagen changes associated with different BCC subtypes compared to normal skin structures and benign lesions. Quantitative analysis such as frequency band energy analysis in Fourier domain, CurveAlign and CT-FIRE fibre analysis was performed on SHG images from 52 BCC and 12 benign lesions samples. Our results showed that collagen distribution is more aligned surrounding BCCs nests compared to the skin's normal structures (p < 0.001) and benign lesions (p < 0.001). Also, collagen was orientated more parallelly surrounding indolent BCC subtypes (superficial and nodular) versus those with more aggressive behaviour (infiltrative BCC) (p=0.021). In conclusion, SHG signal from type I collagen can aid not only in the diagnosis of BCC but could be useful for prognosticating these tumors. Our initial results are limited to a small number of samples, requiring large-scale studies to validate them. These findings represent the groundwork for future in vivo MPM for diagnosis and prognosis of BCC.

Analysis of Surgical Resection of Non-Melanoma Skin Cancer in The Head and Neck of Elderly Population in a Public Hospital of São Paulo

Introduction: Skin cancer is among the most frequent neoplasms worldwide. It is divided into two major groups: non-melanoma skin cancer (NMSC) and melanoma skin cancer (MSC), with NMSC still classified into several subtypes, with the most prevalent being basal cell carcinoma subtype (BCC), followed by squamous cell carcinoma (SCC). Although NMSC does not present high mortality rates, it can involve high morbidity on the functional, aesthetic, and emotional levels. There is a divergence in the literature regarding decision-making in the cases of elderly (patients above 65 years of age) and super elderly patients (starting at 80 years of age). Objectives: This study aims to: 1. Identify the complications of surgical resection of the NMSC of the face and neck in the elderly population. 2. Demonstrate that surgical resection can be used as a therapeutic option in the elderly population without a significantly higher risk of morbidities. Method: This is a transversal, retrospective single-center study of quantitative nature. After the approval of the Research Ethics Committees, analysis was performed on the electronic records of 34 patients who underwent surgery at the Carapicuíba General Hospital between August 2017 and November 2019. The descriptive analysis of the results was performed employing absolute and relative frequency of the qualitative variables; mean and standard deviation were used for the quantitative variables. Analysis of group differences was done through the Fisher's Exact, Student's, or Mann-Whitney T-tests, to evaluate the factors associated with the complications of the procedure. Results: The results showed a mean age of 85.1 years; higher prevalence in females (61.8%); higher prevalence of BCC (76.5%); higher involvement in the nasal (23.5%), periauricular (23.5%), and malar regions (17.7%); hypertension (55.9%), and diabetes mellitus (35.3%) as the main comorbidities; 8 (23.5%) patients had post-surgical complications, and 0 patients had intraoperative complications. Conclusion: It was concluded that surgical resection was a good therapeutic method for the patients approached in the study. It is suggested that the therapeutic choice should be individualized, with the evaluation of the patient as a whole and taking into account aspects other than age group and comorbidities. Moreover, it is necessary to develop new studies and clinical trials with a more significant sample.

Solitary infundibulocystic basal cell carcinoma of lid- A case report and review of literature

The infundibulocystic subtype of Basal cell Carcinoma (IBCC) is a rare entity. It was proposed as a new BCC variant and has been described as a sporadic lesion or as part of Multiple Hereditary Infundibulocysytic BCC(MHIBCC). IBCC in the lids associated with MHIBCC or basal cell naevus syndrome has been reported. However an isolated IBCC of lids has seldom been reported in ophthalmic literature. We report a rare case of solitary IBCC of lids.We report a rare histopathological variant of the commonest lid malignancy, ie BCC.Histopathology of excised lesion of a recuurent chalazion turned out to be IBCC, a rare variant to date reported only as part of MHIBCC. The solitary IBCC, though yet to be reported in lids in ophthalmic literature does exist and ophthalmologists as well as pathologists should be aware of this entity and its less aggressive course.

Immunohistochemical expression of p53, Ki67, α-SMA, CD44 and CD31 in different histological subtypes of basal cell carcinoma.

Basal cell carcinoma (BCC) is a common, locally invasive tumor that arises within sun-damaged skin and rarely develops on the palms and soles or mucous membranes. Men generally have higher rates of BCC than women. Incidence also increases with age and the median age of diagnosis is 68 years old. Mortality from BCC is rare and cases of aggressive, local destructive, metastatic BCCs are more likely from tumors with aggressive histopathological (HP) patterns. The aim of this study was to investigate and correlate the immunohistochemical expression of p53, Ki67, alpha-smooth muscle actin (α-SMA), cluster of differentiation (CD)44 and CD31 with both aggressive and nonaggressive types of BCCs. In our study, we observed a varied staining pattern for p53, with the highest reactivity noticed in the peripheral palisading zone. The staining pattern for Ki67 was similar to p53, with a more pronounced reaction in the periphery of the tumor. We found different Ki67 and p53 expression among the various subtypes of BCC. The CD31 reactivity, mostly seen in the stroma, was positive in all BCCs and varied significantly between its different HP subtypes. Regarding stromal expression of α-SMA, the adenoid and basosquamous types had the most intense reaction in our study. The CD44 tumor expression was correlated in our study to the aggressive pattern of BCCs.

Clinical Clearance Following Improvement of Histologic Subtype of Basal Cell Carcinoma with Sonidegib.

Abstract is missing (Short communication)

A cohort study on detection and subtyping of basal cell carcinoma with optical coherence tomography: The additional value of distant diagnosis by an expert

To the Editor: Optical coherence tomography (OCT), a non-invasive technique for diagnosis of basal cell carcinoma (BCC) could potentially replace standard biopsy, thereby, enabling physicians to diagnose and initiate treatment during the same consultation.1,2 The ability of OCT assessors to discriminate between BCC and non-BCC, and between BCC subtypes (superficial BCC vs non-superficial BCC) must be high. However, the discriminative ability of assessors varies due to differences in experience level.

Recurrence risk of periocular basal cell carcinoma after histologically controlled excision

The incidence of basal cell carcinoma (BCC) has significantly increased in the last decades. The aim of this retrospective study was to determine the risk of recurrence of periocular BCC after histologically controlled resection. Based on the clinical records from 2009-2020 a total of 270 consecutive periocular BCCs from 243 patients were investigated with respect to recurrence after surgical excision. For this study, the type of BCC (primary or recurrent BCC) and localization within the orbital region (upper eyelid nasal, middle, temporal and lower eyelid nasal, middle, temporal) and the histological BCC subtype, e.g. solid/nodular (s/n), superficial multicentric (s-m), infiltrative/sclerodermal (i/s), basosquamous (bsq) and mixed (gem), were recorded. Recurrence rates were compared using χ2-tests. The 270 resected BCCs with 231 primary BCC (pBCC) and 39already recurrent BCC (rBCC), were included in this study. Among the 231 pBCCs we recorded atotal of38 (16.5%, 2‑year recurrence rate 9.2%) recurrences for the abovementioned period. In the 39rBCCs we observed18 (46.2%) recurrences (2-year recurrence rate 37.8%). In addition, asignificantly shorter recurrence-free interval (RFV, ∅ 52.6 ± 9.0months) was observed for the rBCC than for the pBCC (∅108.6 ± 4.1months, p < 0.001). The recurrence rates did not differ significantly with respect to the location; however, there was a significant difference between the five defined subtypes (p = 0.001): s/n = 15.9%, s‑m = 45.0%, i/s = 27.8%, bsq = 33.3% and gem = 40.0%. After R0 resection the recurrence rate of s/n BCC was significantly lower than after R?/R1 resection (p = 0.008). The histological subtypes i/s (p = 0.433), bsq (p = 0.417), and gem (p = 0.143), showed no significant difference between the recurrence rates after R0 and R?/R1 resection. In s‑m BCC, a conclusion on the statistical significance was not possible. The recurrence rate appears to be comparatively high; however, R1 resected BCCs were intentionally included in this study to obtain an evaluation that reflects clinical practice as realistically as possible. It is possible that the surgical procedure and/or the type of histological examination as well as the broad interpretation of the term local recurrence could be the reason for the different recurrence data in the literature. Our data indicate that the recurrence rate is not affected by the exact localization within the orbital region, but by the respective BCC subtype. As recurrences may develop years after BCC excision along-term follow-up is strictly recommended.

870P Systemic levels of the soluble co-inhibitory and co-stimulatory immune checkpoint molecules in basal cell carcinoma

Although co-inhibitory immune checkpoint proteins are primarily involved in promoting inhibitory cell-cell interactions in adaptive immunity, especially tumor immunity, the soluble cell-free variants of these molecules are also detectable in the circulation of cancer patients where they retain immunosuppressive activity. Nevertheless, little is known about the systemic levels of these soluble co-inhibitory immune checkpoints in patients with various subtypes of basal cell carcinoma (BCC), which is the most invasive and treatment-resistant type of this most commonly occurring malignancy.

Combining Reflectance Confocal Microscopy with Optical Coherence Tomography for Noninvasive Diagnosis of Skin Cancers via Image Acquisition.

Skin cancer is one of the most common cancers worldwide. Diagnosis relies on visual inspection and dermoscopy followed by biopsy for histopathological confirmation. While the sensitivity of dermoscopy is high, the lower specificity results in 70%-80% of the biopsies being diagnosed as benign lesions on histopathology (false positives on dermoscopy). Reflectance confocal microscopy (RCM) and optical coherence tomography (OCT) imaging can noninvasively guide the diagnosis of skin cancers. RCM visualizes cellular morphology in en-face layers. It has doubled the diagnostic specificity for melanoma and pigmented keratinocytic skin cancers over dermoscopy, halving the number of biopsies of benign lesions. RCM acquired billing codes in the USA and is now being integrated into clinics. However, limitations such as the shallow depth (~200 µm) of imaging, poor contrast for nonpigmented skin lesions, and imaging in en-face layers result in relatively lower specificity for the detection of nonpigmented basal cell carcinoma (BCCs) - superficial BCCs contiguous with the basal cell layer and deeper infiltrative BCCs. In contrast, OCT lacks cellular resolution but images tissue in vertical planes down to a depth of ~1 mm, which allows the detection of both superficial and deeper subtypes of BCCs. Thus, both techniques are essentially complementary. A "multi-modal," combined RCM-OCT device simultaneously images skin lesions in both en-face and vertical modes. It is useful for the diagnosis and management of BCCs (nonsurgical treatment for superficial BCCs vs. surgical treatment for deeper lesions). A marked improvement in specificity is obtained for detecting small, nonpigmented BCCs over RCM alone. RCM and RCM-OCT devices are bringing a major paradigm shift in the diagnosis and management of skin cancers; however, their use is currently limited to academic tertiary care centers and some private clinics. This paper familiarizes clinicians with these devices and their applications, addressing translational barriers into routine clinical workflow.