Basal Cell Carcinoma Specimens Research Articles

Margin status of basal cell carcinoma: What can be done better?

PurposeGuidelines on clinical margins for basal cell carcinoma (BCC) excisions were recently published, yet ambiguity remains for surgeons and pathologists. The purpose of this study was to determine the incomplete excision rate of BCC, determine factors associated with incomplete excision, and evaluate completeness of reporting between surgeon and pathologist. MethodsA single-centre retrospective analysis was conducted on pathology reports from single excisions of BCC specimens, between January 1, 2019, to December 31, 2020. The primary outcome was incomplete excision rate (positive margins) as reported by pathologist. Logistic regression was used to determine the relationship between incomplete excision rate and anatomical location, pathologist, and surgeon. Completeness of surgeon pathology requisition forms was evaluated qualitatively. ResultsSeven-hundred-and-fifty-six pathology reports were included. The incomplete excision rate was 12% (n=94). The most common site of incomplete excision was head and neck (n=87, 15%), followed by trunk (n=5, 7%), and extremities (n=2, 2%). Five-hundred-and-seventy-nine specimens from 6 surgeons and 9 pathologists were included in the logistic regression analysis. Wald test showed location was significantly associated with incomplete excision (p<0.05), whereas surgeon and pathologist reports were not (p>0.05). Regarding missing information, only 47 (6%) pathology reports included “excision” in the requisition. Four-hundred-and-three (53%) specimens had no clinical history. ConclusionsThe incomplete excision rate found in this study falls within the report range in the literature. Neither surgeon nor pathologist had significant association with incomplete excision. Incomplete excision rate of BCC may be inflated due to lack of standardization in requisition form reporting and pathology reporting.

Récidive des carcinomes basocellulaires palpébraux selon les marges histologiques

Basal cell carcinomas (BCCs) represent 90% of malignant tumors of the eyelids, which can be locally invasive and destructive. The observation of histological safety margins (MHS) allows for the prevention of recurrence while maintaining a fair compromise between aesthetics and functionality. However, to date, there is no consensus or national recommendations concerning the MHS to be observed according to the various histological subtypes of BCCs. Through a retrospective analysis of patient records and corresponding excisional slides, we studied the 6-year recurrence rate of 98 patients who underwent surgery for palpebral BCC. MHS were mostly absent in the excisional specimens of recurrent BCCs and significantly more narrow than in non-recurrent BCCs, on average over 2mm. The results of our study suggest that an average MHS greater than 2mm prevents most recurrences.

Basal Cell Carcinoma in Xeroderma Pigmentosa: Reduced CD1a Expression as a Sensitive Predictor of Recurrence.

Xeroderma pigmentosa (XP) is a rare genetic disorder that is characterized by defective DNA repair after ultraviolet induced damage with a great tendency for recurrent cutaneous malignancies including basal cell carcinoma (BCC). BCC is frequently linked to impaired local immune response with a major role played by Langerhans cells (LCs). The current study aims at investigating LCs in BCC specimens of XP and non-XP patients, in a trial to study its possible impact on tumor recurrence. It included 48 retrospective cases of primary facial BCC (18 for XP patients and 30 for non-XP controls). Each group was subdivided, based on the 5 years follow-up data, into recurrent and non-recurrent BCC groups. LCs were assessed immunohistochemically using the sensitive marker; CD1a. Results showed significantly reduced LCs count (intratumoral, peritumoral, and in perilesional epidermis) in XP patients compared with non-XP controls ( P ˂0.001 for all). Intratumoral ( P =0.008), peritumoral ( P =0.005), and perilesional epidermal ( P =0.02) LCs mean values were significantly lower in recurrent versus non-recurrent BCC specimens. Also, within each group (XP and controls), LCs were of significantly lower means in recurrent versus non-recurrent cases ( P ≤0.001 for all). Regarding recurrent BCC cases, peritumoral LCs showed a significant positive correlation with 1ry BCC duration ( P =0.05). Also, intratumoral and peritumoral LCs correlated positively with BCC relapse interval ( P =0.04 for both). Among non-XP controls, periocular tumors had the least LCs count (22.00±3.56), whereas tumors located in the rest of the face had the greatest count (29.00±0.00) ( P =0.02). Sensitivity and specificity of LCs to predict BCC recurrence in XP patients reached 100% in intartumoral area and perilesional epidermis when cutoff points were less than 9.5 and 20.5, respectively. In conclusion; reduced LC count in primary BCC specimens of XP patients and also in normal subjects could help to predict its recurrence. Thus, it might be identified as a risk factor for relapse to apply new strict therapeutic and preventive measures. This presents new avenue for the immunosurveillance against skin cancer relapse. However, being the first study to investigate that link in XP patients recommends further research to confirm.

Audit of 100 consecutive basal cell carcinoma specimens at a secondary care centre in the UK.

To audit basal cell carcinoma resections against standard guidelines. The retrospective study was done at the Department of Pathology, Sherwood Forest Hospital, Nottinghamshire, United Kingdom, from July 2020 to December 2020 and comprised basal cell carcinoma cases regardless of age and gender. All parameters laid down by the Royal College of Pathologists were matched with the data. Also, incompletely resected specimens were separated, and reasons for incomplete resection were taken into account, and compared with the British Association of Dermatologists 2018 guidelines. Of the 100 consecutive cases, 67(67%) were nodular and nodulocystic, 8(8%) were superficial multifocal, 7(7%) each were infiltrative and mixed nodular and infiltrative, 6(6%) were mixed nodular and superficial, and 5(5%) were mixed superficial and infiltrative. All 100(100%) pathology reports contained the mandatory information set by the Royal College of Pathologists. There were 7(7%) incompletely excised cases. The rate of incomplete excision was also within the acceptable range defined by the British Association of Dermatologists 2018 guidelines. All basal cell carcinoma resections were in line with the standard guidelines.

Evaluation of nestin expression in melanoma, basal cell carcinoma and basosquamous carcinoma

Introduction: Nestin plays a significant role in diagnosis, prognosis, clinical course and/or response to the treatment. Previous studies have investigated the nestin expression in melanoma, however a limited number have focused on basal cell carcinoma (BCC) and basosquamous carcinoma (BSC). Objectives: The current study aimed to investigate nestin expression in melanoma, BCC, and BSC. Materials and Methods: This cross-sectional study was conducted on 40 melanomas, 40 BCC and 40 BSC specimens. Tumor size, lesion location and stage of disease were recorded. Then, nestin staining was conducted in all the present samples, then the amount of nestin expression was assessed. Results: According to the results of this study, nestin was expressed in all melanoma specimens; while it was expressed in 15% of BSC and 25% of BCC specimens. The mean score of nestin expression in melanoma specimens (0.85 ± 2.50) was significantly higher than the BSC and BCC specimens with the means of 0.36±0.15 and 0.44±0.25 respectively (P value &lt;0.001). However, there was no significant difference between BSC and BCC specimens in nestin expression. Additionally, in the melanoma specimens, a significant and direct relationship between nestin expression and the various stages of melanoma with the coefficient of 0.345 (P value = 0.025). Conclusion: The results of the current study showed that expression of nestin could have a good prognostic value in skin melanoma while, there is a significant relationship with its progression. However, in non-melanoma specimens, no distinction can be detected regarding the nestin expression.

MOC-31 Antibody Immunolabeling During Mohs Surgery.

Ber-EP4 is an antibody that labels basal cell carcinoma (BCC) by targeting epithelial cell adhesion molecule (Ep-CAM). MOC-31, a monoclonal mouse antibody, also targets Ep-CAM and is currently used to differentiate several extracutaneous epithelial tumors. However, the utility of MOC-31 has not been fully described in cutaneous tumors and in Mohs micrographic surgery (MMS). To evaluate MOC-31 labeling in BCC and other cutaneous tumors and to compare immunolabeling intensity of MOC-31 and Ber-EP4 in BCCs. Nineteen permanently fixed and 29 frozen BCC specimens and 23 other cutaneous tumors were labeled with MOC-31; labeling intensity of tumors, epidermis, and adnexal structures were recorded. In a separate study, a blinded dermatopathologist compared labeling intensities of 8 BCC specimens, each labeled with MOC-31 and Ber-EP4.4. MOC-31 labeled all BCCs. Eccrine coils and follicular bulbs did label variably, although this did not detract utility of MOC-31. Five of thirteen cutaneous squamous cell carcinomas and one of two Merkel cell carcinomas demonstrated MOC-31 positivity. MOC-31 and Ber-EP4 labeled BCCs similarly. MOC-31, an antibody directed against Ep-CAM, is sensitive for BCCs in frozen specimens encountered in MMS and permanently fixed specimen. In addition, MOC-31 demonstrated comparable immunolabeling characteristics with Ber-EP4 for BCCs.

Melanocytes as the source of the increased melanisation in pigmented epithelial tumours: a holistic approach.

We aimed to elucidate the causes of the increased melanisation in basal cell carcinoma (BCC) and seborrheic keratosis (SK), and the role of melanocytes in this process. This study was a retrospective-cohort study conducted in the pathology department of a university hospital between January 2019 and October 2020. Forty-nine SK and 30 pigmented BCC were included in our study. SRY-box transcription factor 10 (SOX10), CD68, and Masson-Fontana staining was used for analysis in all samples. A representative section of each specimen was photographed under ×400 magnification to facilitate the assessments of the morphology of the melanocytes and their following morphometric parameters: density, nuclear diameter, and distribution. The density of pigmented keratinocytes in the lesional epidermis was scored. The nuclear diameters of melanocytes located in the nonlesional epidermis, the density of the melanophages, and the presence or absence of ulceration and solar elastosis were also recorded. The morphometric findings confirmed a statistically significant increase in melanocyte density in the BCC group compared with that in the SK group (p < 0.001). Moreover, the nuclear minor diameters in the melanocytes of the BCC sections were significantly higher than those in the SK specimens (p < 0.001). The epidermal melanocytes were distributed diffusely in almost all BCC specimens (96.7%), whereas they were mainly limited to the basal layer in the majority of the SK sections (59.2%). The number of epidermal melanised keratinocytes with a score of 3 was significantly higher in the SK group (n = 31; 63.2%) than in the BCC group (n = 6; 20%) (p = 0.001), and they were the main cells representing the pigmented appearance of the tumours. No significant difference was found between both tumour groups in terms of their melanophage density scores (p = 0.206). This study is the first step towards an objective quantification of the melanocytes in pigmented epithelial tumours and may provide a morphological background for future studies on these skin lesions.

Combined PARP1-Targeted Nuclear Contrast and Reflectance Contrast Enhance Confocal Microscopic Detection of Basal Cell Carcinoma.

Reflectance confocal microscopy (RCM) with endogenous backscattered contrast can noninvasively image basal cell carcinomas (BCCs) in skin. However, BCCs present with high nuclear density, and the relatively weak backscattering from nuclei imposes a fundamental limit on contrast, detectability, and diagnostic accuracy. We investigated PARPi-FL, an exogenous nuclear poly(adenosine diphosphate ribose) polymerase (PARP1)-targeted fluorescent contrast agent, and fluorescence confocal microscopy toward improving BCC diagnosis. Methods: We tested PARP1 expression in 95 BCC tissues using immunohistochemistry, followed by PARPi-FL staining in 32 fresh surgical BCC specimens. The diagnostic accuracy of PARPi-FL contrast was evaluated in 83 surgical specimens. The optimal parameters for permeability of PARPi-FL through intact skin was tested ex vivo on 5 human skin specimens and invivo in 3 adult Yorkshire pigs. Results: We found significantly higher PARP1 expression and PARPi-FL binding in BCCs than in normal skin structures. Blinded reading of RCM-and-fluorescence confocal microscopy images by 2 experts demonstrated a higher diagnostic accuracy for BCCs with combined fluorescence and reflectance contrast than for RCM alone. Optimal parameters (time and concentration) for PARPi-FL transepidermal permeation through intact skin were successfully determined. Conclusion: Combined fluorescence and reflectance contrast may improve noninvasive BCC diagnosis with confocal microscopy.

Melanocytic hyperplasia associated with surgical scars in basal cell carcinoma re‐excision specimens: A single‐center retrospective study

Melanocytic hyperplasia (MH) overlying surgical scars has been reported but MH adjacent to the scar has not been previously addressed. We evaluated scar-associated MH in 489 re-excision specimens of basal cell carcinoma. Melanocytic density, confluence, atypia, suprabasal scatter, follicular extension, distance from the scar, correlation with clinicopathologic parameters, and PRAME expression were recorded. One hundred seventy-seven of 489 (36%) cases exhibited MH beyond the scar extending to 6.65 mm median distance, with a median density of 13 melanocytes/0.5 mm (6-24 mm), confluence in 74 (42%) cases, atypia in 14 (8%), suprabasal melanocytes in 25 (14%), and follicular extension in 21 (12%). Mean age of MH group was significantly lower than non-MH group (P< 0.0001). MH overlying the scar was significantly higher in specimens with elastosis than those without elastosis (P< 0.0001). PRAME expression was absent in 14 of 20 cases and present in rare melanocytes in 6 cases. Increased melanocytic density with confluence, mild atypia, suprabasal scatter, and superficial follicular extension may be observed in re-excision specimens adjacent to surgical scars in the absence of a melanocytic neoplasm. These observations are helpful for appropriate interpretation of melanoma re-excision specimens, to avoid potential pitfalls in diagnosis and unnecessary therapeutic measures.

Cytotoxic T-Lymphocyte-Associated Protein-4 and Lymphocyte Activation Gene-3 Expression in Orbitally-Invasive Versus Nodular Basal Cell Carcinoma.

To compare the expression of cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) and lymphocyte activation gene-3 (LAG-3) in nodular and orbitally-invasive forms of basal cell carcinoma (BCC). Immunohistochemical staining for CTLA-4 and LAG-3 was performed on the pathology specimens of BCC from orbital exenteration and nodular forms. The numbers of positively-staining cells/×40 field were counted across 5 consecutive fields of each specimen and statistical analysis was performed to calculate the difference in expression between the 2 groups. Nine cases of orbitally-invasive BCC and 6 cases of nodular BCC were studied. The mean numbers of CTLA-4-positively staining cells were 11.51 cells/×40 field (median = 6.60 cells/×40 field, range = 0.4-31.8 cells/×40 field) in invasive BCC and 0.90 cells/×40 field (median = 0.60 cells/×40 field, range = 0.0-2.8 cells/×40 field) in nodular specimens. The difference between the 2 groups was statistically significant (p = 0.0030). The mean number of LAG-3-positively staining cells was 0.58 cells/×40 field (median = 0.0, range = 0.0-2.8 cells/×40 field) in invasive BCC and 3.13 cells/×40 field (median = 0.0, range = 0.0-18.18 cells/×40 field). There was no significant difference in LAG-3 positivity between tumor groups (p = 0.5564). CTLA-4 expression was enriched in orbitally invasive BCC compared with nodular forms of BCC, whereas LAG-3 expression did not differ between these entities. CTLA-4 mediated immune suppression may facilitate the development of orbitally invasive BCC. Treatment strategies that use existing medications to target CTLA-4 may decrease the requirement for orbital exenteration and provide enhanced survival outcomes.

Expression of thymidylate synthase in salivary adenoid myoepithelial cells and its clinical significance

To evaluate the expression of thymidylate synthase (TS) in myoepithelial cells (MECs) of salivary adenoid tissues and explore its clinical significance. Immunohistochemical staining EnVision method was used to detect the expression of TS, P63, Calponin, CK5/6 and S-100 in 32 salivary gland specimens, including 10 non-neoplastic and salivary inflammation specimens, 11 mixed tumor specimens, 5 basal cell carcinoma specimens and 6 adenoid cyst carcinoma specimens. The specificity and sensitivity of TS as a specific molecular marker of salivary muscle epithelial cells were evaluated in comparison with P63, Calponin, CK5/6 and S-100. The expression pattern of TS in all the salivary gland tissue specimens was identical with that of p63. TS and P63 both showed strong immunohistochemical expressions in MECs of salivary adenoid tissue specimens. Calponin, CK5/6, and S-100 showed cytoplasmic/membranous expressions in the MECs. In addition, TS exhibited weak or moderate cytoplasmic expression in a few salivary gland epithelial cells, cancer cells and scattered stromal cells, with negative expression in the cell nuclei. The expression of TS in the MECs of all the salivary adenoid specimens was highly consistent with those of P63, Calponin, CK5/6 and S-100 (P&gt;0.05) Except for CK5/6 expression in Salivary inflammation and Salivary gland specimens. Kappa&gt;0.75. The specificity and sensitivity of TS as a molecular marker of MECs were both 100%. TS is a new specific marker of MECs for differential diagnosis of salivary gland tumors.

Recommended Surgical Margins for Basal Cell Carcinoma: Is 3 mm Safe Enough?

The primary aim of treatment of basal cell carcinoma (BCC) is the complete excision of the tumor. Reconstruction of the defect after surgical excision varies, depending on the location and size of the defect and the skin to be used in the reconstruction. In this study, investigators compared the rates of tumor positivity at the edges of BCC specimens excised with 3- or 5-mm surgical margins. Researchers analyzed data related to 113 patients with a preliminary diagnosis of BCC between August 2016 and June 2018. In total, 99 lesions from 91 patients not exceeding 2 cm in size excised with 3-mm (n = 53) or 5-mm (n = 46) surgical margins were included. Statistical analysis was performed using the χ test. After histopathologic assessment, 3 of 53 lesions that were excised with 3-mm surgical margins had a positive surgical margin, whereas none of the 46 lesions excised with 5-mm margins indicated a positive tumor presence. However, there was no statistical difference between the groups. A 3-mm surgical margin may be sufficient and safe for BCC excision.

Nondestructive Evaluations of Melanin-related Compounds in the Skin Using Electron Paramagnetic Resonance and Permeability Measurements.

Melanin-related compounds in paraffin-embedded tissue specimens of basal cell carcinoma (BCC), seborrheic keratosis (SK), malignant melanoma (MM), and nevus pigmentosus (NP) were nondestructively investigated using permeability measurements (light penetration into pigmented lesion), X-band (9.4 GHz) electron paramagnetic resonance (EPR), and EPR imaging (EPRI). The paramagnetic species in BCC, SK, MM, and NP specimens were analyzed using intensity, linewidth, spectral pattern, and X-band EPRI. The EPR spectra of BCC, SK, and NP showed a single line pattern. The EPR signal intensities of the BCC, SK, and NP samples corresponded to the permeability values that are directly related to pigment color tone, except for MM. The correlation coefficient between EPR and permeability was supported by the high degree of linear relation in the range. We further analyzed MM and speculated that MM contains an additional signal of the pheomelanin radical. In MM and NP samples, two-dimensional (2D) EPRI revealed paramagnetic species distribution and different magnitudes. The paramagnetic (radical) species are directly related to the pigmented lesion site. To conclude, spectroscopic analyses suggest that pheomelanin-related compounds may exist in malignant melanoma.

Comparison of nonlinear microscopy and frozen section histology for imaging of Mohs surgical margins.

Mohs surgery uses en face frozen section analysis (FSA) with complete margin examination for the excision of select basal cell carcinomas (BCC), obtaining excellent cosmetic outcomes and extremely low recurrence rates. However, Mohs with FSA is time-consuming because of the need to iteratively perform cryosectioning on sequential excisions. Fluorescent microscopies can image tissue specimens without requiring physical sectioning, potentially reducing the time to perform Mohs surgery. We demonstrate a protocol for nonlinear microscopy (NLM) imaging of surgical specimens that combines dual agent staining, virtual H&E rendering, and video rate imaging. We also introduce a novel protocol that enables micron-level co-registration of NLM images with FSA histology, and demonstrate that NLM can reproduce similar features similar to FSA in BCC specimens with both negative and positive surgical margins. We show that the fluorescent labels can be extracted with conventional vacuum infiltration processing, enabling subsequent immunohistochemistry on fluorescently labeled tissue. This protocol can also be applied to evaluate the performance of NLM compared with FSA in a wide range of pathologies for intraoperative consultation.

Investigation of Paraffin-embedded Basal Cell Carcinoma Using Electron Paramagnetic Resonance.

Basal cell carcinoma (BCC) in paraffin-embedded specimens was investigated by nondestructively electron paramagnetic resonance (EPR) and X-band (9.45 GHz) EPR imaging (EPRI). A histopathological examination of specimens showed the melanin contents and revealed that they were predominantly of the nodular types. A single-line EPR pattern was observed in the BCC specimens, and the spectra of the samples were analyzed using linewidth and spectral pattern parameters. The eumelanin-related radical was observed in paraffin-embedded BCC specimens. The stability of the radical was supported by sepia pigment experiments. The g-value and peak-to-peak linewidths (ΔHpp) were 2.0046 and 0.61 ± 0.02 mT (mean ± SEM), respectively. Strong EPRI signals correspond to areas of strong pigmentation in the samples. Thus, histopathological examination, EPR, and EPRI of BCC specimens showed that the radical distribution reflects on the spatial distribution of pigments in the samples.

Evaluation of p53 and Ki67 Expression Profiles in Basal Cell Carcinomas in a Usual and an Unusual Location.

Owing to their importance in cell proliferation in cutaneous malignancies, we aimed to immunohistochemically compare the expression profiles of p53 and Ki67 in basal cell carcinoma (BCC) cases in both a usual and an unusual locations in this study. In this study we included 12 in an unusual location of BCC cases and 21 BCC cases in a usual location. Immunohistochemical expression of p53 and Ki67 antibodies were studied in 33 paraffin-embedded tissue specimens of basal cell carcinoma. We compared the p53 and Ki67 staining scores with clinicopathologic features. The tumor size was found to be greater in BCC cases in an unusual location than those in a usual location. The relationship between age and tumor size was also evaluated in both groups and it was found that tumor size increased with age. A comparative study between the two groups showed no difference p53 and Ki67 expression percentages. There was a linear correlation between the Ki67 and p53 marker staining rates (ρ=0.420; p=0.015). In the samples taken from cases in a usual region, there was a linear and moderate relationship between the markers (ρ=0.513; p=0.017). Median tumor diameter results were similar to the marker staining score (p > 0.05). This is the first study comparing the expression profiles of p53 and Ki67 of BCC cases in an unusual and a usual location. No significant difference was found concerning Ki67 and p53 expression levels between the two groups.

Clinicopathological Pattern of Basal Cell Carcinoma among Sudanese Patients

Background: Basal cell carcinoma (BCC) is a frequently diagnosed skin cancer with variable histopathological types. BCC was not widely studied in Sudan as it is in the Caucasian population. Objectives: To appraise the clinical and histopathological aspects of BCC of the skin in Sudan. Materials and methods: A retrospective descriptive analysis of 84 histologically diagnosed BCC specimens seen at three hospitals in four-year duration were reviewed and classified into histological variants according to the WHO classification 2006. Data were analyzed using Statistical Package for the Social Sciences, version 23.0. Results: The mean age (±SD) of the study participants was 56 (±1.75) years, ranging from 20 to 92 years and 63.1% were females (Female to male ratio 1.7:1). The most common incidence was among the age group 51 - 60 years. The face was the primary tumor site in 89.3% with a predilection for the nasal area (31% of those in the face), followed by the trunk (6%). Out of the total, 54.8% were histologically categorized as nodular/solid, while infiltrative accounts for 11.9% followed by the superficial type (8.3%). Surgical margins were involved in 34.5% of cases and peri-neural invasion was seen in 3.6% of cases, mostly were of the infiltrative variant. Conclusion: BCC in Sudan is commonly present in the head as solid nodular histopathological variant which is correlated with worldwide distribution but has slightly younger age and female predominance; thus further studies are needed to assess risk factors in Sudanese patients and improve approaches for earlier diagnosis and better management.

Marking sutures to orientate specimens of basal cell carcinoma: do they really make a difference?

Traditionally, marking sutures have been used to orientate specimens of non-melanomatous skin cancers, and they provide an identifiable point as a reference for monitoring and further treatment. For histopathological purposes, the orientated specimen is marked with different inks, which enables measurement to the nearest lateral and deep margins, and if invaded, guides further excision. We retrospectively analysed 688 specimens of basal cell carcinoma (BCC) from the head and neck from two separate years: 2010 and 2012. Marking sutures were used in 663 (96%) cases. There were 21 invaded margins (3%), 17 (81%) at the lateral margin and 4 (19%) at the deep margin. Of the 17 with invaded lateral margins, 10 were from the nose, and the remaining 7 from other sites including the ear (n=2), and neck, forehead, temple, eyelid, and cheek (n=1 each). Of the 663 marked specimens, the marking stitch was useful in only one patient who needed another operation (0.2%). We suggest that routine orientation of BCC, even from high risk areas, is not necessary. If the operating surgeon questions the size of the margin when a lesion is ill-defined or of a high-risk histological subtype, then excision with monitored en-face margins should be considered with traditional Mohs surgery or a reliable modified version.

Effects of Combined Treatment With Arsenic Trioxide and Itraconazole in Patients With Refractory Metastatic Basal Cell Carcinoma.

Tumor resistance is an emerging problem for Smoothened (SMO) inhibitor-treated metastatic basal cell carcinoma (BCC). Arsenic trioxide and itraconazole antagonize the hedgehog (HH) pathway at sites distinct from those treated by SMO inhibitors. To determine whether administration of intravenous arsenic trioxide and oral itraconazole in patients with metastatic BCC is associated with a reduction in GLI1 messenger RNA expression in tumor and/or normal skin biopsy samples. Five men with metastatic BCC who experienced relapse after SMO inhibitor treatment underwent intravenous arsenic trioxide treatment for 5 days, every 28 days, and oral itraconazole treatment on days 6 to 28. Data were collected from April 10 to November 14, 2013. Follow-up was completed on October 3, 2015, and data were analyzed from June 5 to October 6, 2015. The primary outcome was the change in messenger RNA levels of the GLI family zinc finger 1 (GLI1) gene (HH-pathway target gene) in biopsy specimens of normal skin or BCC before and after treatment. Secondary objectives were evaluation of tumor response and tolerability. Of the 5 patients (mean [SD] age, 52 [9] years; age range, 43-62 years), 3 completed 3 cycles of treatment and 2 discontinued treatment early owing to disease progression or adverse events. Adverse effects included grade 2 transaminitis and grade 4 leukopenia with a grade 3 infection. Overall, arsenic trioxide and itraconazole reduced GLI1 messenger RNA levels by 75% from baseline (P < .001). The best overall response after 3 treatment cycles was stable disease in 3 patients. Targeting the HH pathway with sequential arsenic trioxide and itraconazole treatment is a feasible treatment for metastatic BCC. Although some patients experienced stable disease for 3 months, none had tumor shrinkage, which may be owing to transient GLI1 suppression with sequential dosing. Continuous dosing may be required to fully inhibit the HH pathway and achieve clinical response.

Combined reflectance confocal microscopy-optical coherence tomography for delineation of basal cell carcinoma margins: an ex vivo study.

We present a combined reflectance confocal microscopy (RCM) and optical coherence tomography (OCT) approach, integrated within a single optical layout, for diagnosis of basal cell carcinomas (BCCs) and delineation of margins. While RCM imaging detects BCC presence (diagnoses) and its lateral spreading (margins) with measured resolution of ∼1 μm, OCT imaging delineates BCC depth spreading (margins) with resolution of ∼7 μm. When delineating margins in 20 specimens of superficial and nodular BCCs, depth could be reliably determined down to ∼600 μm, and agreement with histology was within about ±50 μm.