Nodular Basal Cell Carcinoma Research Articles

Deep Learning for Automated Segmentation of Basal Cell Carcinoma on Mohs Micrographic Surgery Frozen Section Slides.

Deep learning has been used to classify basal cell carcinoma (BCC) on histopathologic images. Segmentation models, required for localization of tumor on Mohs surgery (MMS) frozen section slides, have yet to reach clinical utility. To train a segmentation model to localize BCC on MMS frozen section slides and to evaluate performance by BCC subtype. The study included 348 fresh frozen tissue slides, scanned as whole slide images, from patients treated with MMS for BCC. BCC foci were manually outlined using the Grand Challenge annotation platform. The data set was divided into 80% for training, 10% for validation, and 10% for the test data set. Segmentation was performed using the Ultralytics YOLOv8 model. Sensitivity was .71 for all tumors, .87 for nodular BCC, .79 for superficial BCC, .74 for micronodular BCC, and .51 for morpheaform and infiltrative BCC. Specificity was .75 for all tumors, .59 for nodular BCC, .58 for superficial BCC, .83 for micronodular BCC, and .74 for morpheaform and infiltrative BCC. This study trained a segmentation model to localize BCC on MMS frozen section slides with reasonably high sensitivity and specificity, and this varied by BCC subtype. More accurate and clinically relevant performance metrics for segmentation studies are needed.

Frequent Occurrence of High-Risk Basal Cell Carcinoma in Xeroderma Pigmentosum: A Histopathological Insight From an Indian Cohort.

Xeroderma pigmentosum (XP) is a genodermatosis, characterized both by premature aging and significantly increased risk of non-melanoma and melanoma skin cancers at an early age. However, limited literature is available on the common histopathological subtypes of basal cell carcinoma (BCC) in these patients. In this ambispective case series, we recruited patients of XP who had either a currently present skin tumor or previously excised one, provided their histopathological sections were available. Cytogenetic analysis was performed in all the patients. The histopathological findings were recorded by two trained dermatopathologists. Of 22 recruited patients with XP, 12 patients had 41 BCCs, and 23 (56.09%) of them showed a high-risk histopathological subtype. Basosquamous carcinoma (10, 24.39%) was the most frequent high-risk tumor followed by infiltrative variant (7, 17.07%). Mixed-histopathological subtypes were noted in six (14.63%) cases, and all of them had a high-risk component. The low-risk subtypes included nodular (n = 17, 41.46%) and superficial BCC (1, 2.43%). Though a deep dermal involvement was seen in 27 (65.85%) lesions, none showed a perineural invasion or necrosis. Three (7.31%) lesions showed ulceration, while 10 (24.39%) showed presence of pigmentation. A frequent occurrence of high-risk basal cell carcinoma was noted in patients with XP-mandating creation of appropriate treatment and follow-up strategies in these patients.

Effective Treatment of Basal Cell Carcinoma with a Topical Enzymatic Mixture Enriched in Bromelain: Summary of Proof-Of Concept Clinical Studies on the First 22 Tumors.

Background/Objectives: Basal cell carcinoma (BCC), the most prevalent form of human cancer, is traditionally treated by surgical and alternative destructive or topical chemical means, each with its advantages, challenges, and drawbacks. We describe our experience treating BCCs with a topical concentrate of proteolytic enzymes enriched in bromelain (CPEEB) sourced from pineapple stems. CPEEB has strong proteolytic, antitumor-proapoptotic, and inflammation modulation activities, and is approved for debridement of deep burns and starting phase 3 trials for chronic wounds. Methods: In the first proof-of-concept (POC) study, six BCCs on three individuals were treated with five to six daily CPEEB 10% topical applications under a zinc oxide-based occlusive dressing for 9-12 h each during a period of up to 10 days. These patients were followed for up to 4 years. In an additional two POC studies, 16 patients with one BCC each were treated every other day for a total of seven applications of topical CPEEB 5% under a variety of occlusive dressings. The wounds were followed for up to 2 months before undergoing diagnostic excisional biopsy. Results: In the first study, clinical assessment of the BCCs and two excisional biopsies after 6 months suggested that all lesions were eradicated with spontaneous healing within ~2 weeks without clinical or histological recurrence for over 4 years. In the two subsequent studies, 16 histologically diagnosed superficial and nodular BCCs were treated using four application techniques. Excisional histology after 2 months confirmed BCC eradication in seven of the patients. In nine patients, with compromised occlusive dressings, histological eradication was incomplete. Treatment was well tolerated by all patients with the expected local skin reactions, which completely healed within 2-3 weeks. Conclusions: These are POC preliminary studies aimed at indicating the potential efficacy and feasibility of topical CPEEB in eradicating BCC. In these studies, topical CPEEB 10% and 5% resulted in complete eradication of the BCC when appropriately applied. CPEEB was well tolerated in all patients, and all treated sites' erosions healed without scars in <3 weeks. Further research is necessary to corroborate the results, refine the application technique, and complete the regulatory process.

Nodular basal cell carcinoma of the scrotum: a case report and review of the literature

Nodular basal cell carcinoma of the scrotum: a case report and review of the literature

Basal Cell Carcinoma Cleft: The Missing Piece of the Puzzle.

This study aims to explore the tumor-stroma separation or the cleft characterizing basal cell carcinoma (BCC). In this retrospective cohort investigation, we enrolled 244 patients who received a confirmed diagnosis of BCC through histopathological examination in the period of 2019-2020 at the Pathology Laboratory of the "Sfântul Apostol Andrei" Emergency Clinical Hospital located in Galați, Romania. The identification of patients was accomplished by utilizing electronic health records, and relevant clinical, demographic, and histopathological data were retrieved from the physical database of the Pathology Laboratory. Key tumor characteristics were gathered, and an in-depth analysis of case slides was performed. The average tumor-stroma cleft's width measurement was 48.136 µm, while its respective tumor island's width was on average 952.587 µm. The cleft's width and its respective tumor island's width are dependent on the BCC subtype, just like the ratio between the tumor island's measurement and its cleft's width are, being larger in basosquamous BCC, micronodular BCC, infiltrative BCC, and morpheaform BCC. The BCC tumor islands were found to have a minimal approximately equal measurement to the tumor-stroma separation cleft, but they were always larger than the latter. Large clefts and their respective tumor islands were found in specific tumor subtypes such as basosquamous BCC, micronodular BCC, infiltrative BCC, and morpheaform BCC, but in nodular BCC also.

Surgical Reconstruction in Malignant Eyelid Tumors.

To report the histopathological subtypes of malignant eyelid tumors treated surgically in the author's clinic and to present the author's graft and flap preferences in the reconstruction of the eyelid defect after surgical excision. This retrospective study included 33 patients who underwent malignant eyelid tumor excision, followed by eyelid reconstruction. A frozen section was performed during surgery to assess surgical margins in all patients. Demographic characteristics, histological classification, localization, and size of the tumor, postoperative defect size, follow-up period, complications, and recurrence rate were recorded. Of the patients with a mean age of 66.6 ± 15.3 (range: 23-94), 15 (45.5%) were females and 18 (54.5%) were males. The lower eyelid was the most commonly involved site in 27 (81.8%) patients. Basal cell carcinoma was the most frequently diagnosed type of malignant cancer in 81.8% (n = 27) of the cases. Among the tumor subtypes, nodular type basal cell carcinoma was the most frequently observed subtype in 10 (30.3%) patients. Wide excision with different flap and graft techniques was performed in 26 (78.8%) patients with defect sizes of 40% or larger. In the author's study, the most preferred flap technique for anterior lamella reconstruction was the Tenzel semicircular flap (30.3% n = 10). The most frequently preferred flap for posterior lamella reconstruction was the Hughes tarsoconjunctival flap (30.3% n = 10). There were no flap or graft failures in any of the author's cases. In the treatment of malignant eyelid tumors, different local flap and graft techniques selected according to the size of the defect have successful anatomical results in reconstructive surgery after frozen section controlled excision.

Lip lift with advancement flap as nasal columella reconstruction

Basocellular carcinomas are characterized by their non-deep spread neoplastic nature. Although treatment typically proceeds without complication, excision in critical facial regions can lead to aesthetically undesirable defects. Furthermore, elderly patients often express aesthetic concerns, particularly regarding the thinning of the upper lip over time. This article presents the case of a 75-year-old patient with a basocellular carcinoma located on the tip of the nose, amidst a history of multiple neoplastic conditions. To address the defect, an inferiorly-based philtral advancement flap was employed, accompanied by a lip lift procedure, resulting in favorable aesthetic and functional outcomes.

Diffuse infiltrative basal cell carcinoma of the eyelid in an adolescent; a rare entity and its atypical presentation

Basal cell carcinoma (BCC) is the most common malignancy of the eyelids in the West; however, BCC is less common among Asians (11%–65%). Although it is prevalence among the elderly, it is rare in adolescents. Herein, we report a case of a 17-year-old boy who presented with a diffuse, irregular mass on the right lower eyelid, persisting for one year, with no associated ocular complaints. Further clinical evaluation revealed a diffuse, infiltrating lesion involving the lower lid and palpebral conjunctiva, an inflamed ocular surface, and a pigmented lesion along the lateral border of the lower eyelid, accompanied by the loss of lid architecture and cilia. The lesion was associated with symblepharon medially and fixation to the underlying tissue. Systemic examination was clinically unremarkable. An incision biopsy confirmed the diagnosis of basal cell carcinoma. The lesion was further managed by excision biopsy with a 4 mm margin, which revealed conjunctival extension on histopathological examination. A tumor-free margin was obtained after a deep excision, followed by further histopathological analysis. The defect was covered with an amniotic membrane graft, and no signs of recurrence were noted after an 8-month follow-up.

Immunotherapy in Basal Cell Carcinoma.

Basal cell carcinoma (BCC) is the most frequent of all cancers, with an increasing incidence. The first line therapy is surgical excision, but topical therapies can be used in low-risk superficial BCCs, while the more advanced, unresectable, or metastatic BCCs benefit from systemic therapies with hedgehog inhibitors and immunotherapy. The purpose of this review is to highlight local and systemic immunotherapies and their efficacy in the management of BCCs. Local therapies can be considered in superficial and low-risk nodular BCCs, with imiquimod frequently used for its antitumor and immunoregulatory properties. Imiquimod alone demonstrated higher histological clearance rates, but patients treated with imiquimod experienced more adverse events than ones treated with other therapies. Imiquimod can be used as an adjuvant before Mohs micrographic surgery and can also be combined with other local therapies, like curettage, electrodesiccation, cryosurgery, and photodynamic therapy, with some treatment methods yielding results comparable with the surgery. Interferons and Interleukin-2 were evaluated in a small number of studies with different results. Systemic immunotherapies with programmed death-ligand 1 (PD-L1) inhibitors showed inconsistent results in patients with advanced BCCs, being effective in some patients that progressed on or were intolerant to hedgehog pathway inhibitors (HHI).

Inherited Basaloid Neoplasms Associated With SUFU Pathogenic Variants.

Germline SUFU pathogenic variants (PVs) have previously been associated with basal cell nevus syndrome (BCNS) and multiple infundibulocystic basal cell carcinoma syndrome; however, a broader spectrum of cutaneous findings in patients with SUFU PVs has not been well delineated. To define the clinical and histopathologic spectrum of cutaneous findings in patients with germline SUFU PVs. This case series was conducted in multiple US academic dermatology, medical genetics, and medical oncology clinics between July 2014 and July 2022. The study included patients with confirmed germline SUFU PVs who were evaluated by a dermatologist. The analysis took place from March to September 2023. Histopathologic evaluation of skin biopsies with or without immunohistochemical staining, and targeted next-generation sequencing (NGS) on tumor specimens. All 5 patients were women. The mean (range) age at presentation was 50.2 (31-68) years, with skin manifestations initially appearing in the fourth to sixth decades of life. None had keratocystic odontogenic tumors. A total of 29 skin pathology specimens from the 5 patients were reviewed; of these, 3 (10.3%) were diagnosed as basaloid follicular hamartomas (BFHs), 10 (34.5%) classified as infundibulocystic basal cell carcinomas (iBCCs), 6 (20.7%) classified as nodular basal cell carcinomas (nBCCs), and 1 (3.4%) as infiltrative basal cell carcinoma (BCC). Targeted NGS studies on tumor specimens suggest that an increased number of UV-signature variants is associated with basal cell carcinomas compared with more indolent basaloid follicular hamartomas. Patients with germline SUFU PVs may present with multiple indolent basaloid neoplasms in addition to conventional basal cell carcinomas, typically appearing in the fourth to sixth decades of life. Although there are overlapping clinical manifestations, these findings help to differentiate the clinical syndrome associated with SUFU PVs from PTCH1 BCNS. Awareness of the clinicopathologic spectrum of SUFU-associated basaloid neoplasms is important for dermatologists and dermatopathologists because many (although not all) of these lesions are indolent and do not require aggressive surgical treatment. Importantly, because SUFU lies downstream of the protein smoothened, vismodegib and other smoothened inhibitors are unlikely to be effective therapies in this subset of patients.

A case of basal cell carcinoma of skin with bone metastasis: a case report

BackgroundBasal cell carcinoma is the most prevalent skin cancer, most characterized by local aggressiveness but with low metastatic potential, and bone metastasis is quite heterogeneous, thus the incidence profile is variable size from 0.0028% to 0.5%. We have this patient with an unusual example of basal cell carcinoma with bone metastases to add to the scarce report on this matter.Case descriptionHere we document a 48-year-old Persian man with a background of being exposed to the sun for a long time. He was diagnosed with an ulcer on the cheek, which was clinically characterized and further confirmed by biopsy as morpheaform basal cell carcinoma. Following the first round of excision, multiple relapses eventually metastasized to the bone. The latter was found on follow-up radiologic scans. This case is characterized by the aggressive nature of the disease and the heterogeneity of basal cell carcinoma growth, thus challenging the conventional view of basal cell carcinoma behavior. Treatment included surgical excision of the primary lesion, which was treated with radiotherapy afterward. However, the skeleton improved slowly during follow-up, and palliative care was eventually pursued to control symptoms and improve quality of life.ConclusionsThis was a rare case of basal cell carcinoma metastasis to non-bone organs, which reminded us to consider basal cell carcinoma metastasis, especially in the case of atypical basal cell carcinoma. Therefore, risk-aware patient management is essential. Moreover, these findings highlight the role of further research into the mechanisms of basal cell carcinoma metastasis, leading to improved therapeutic strategies that may lead to potential improvements in patient outcomes.

Application of Ultraviolet-Enhanced Fluorescence Dermoscopy in Basal Cell Carcinoma.

Basal cell carcinoma (BCC) is the most common non-melanoma skin cancer. The aim of the current study was to analyze the ultraviolet-enhanced fluorescence dermoscopy (UVFD) characteristics of BCCs. BCCs were evaluated under polarized dermoscopy (PD) and UVFD. The findings in PD were described using predefined parameters for dermoscopic evaluation in dermato-oncology. UVFD characteristics were determined based on personal observations, and included interrupted follicle pattern, absence of pink-orange or blue-green fluorescence, well-demarcated borders, and dark silhouettes. In total, 163 BCCs were analyzed. Under UVFD, the interrupted follicle pattern (p < 0.001), absence of pink-orange fluorescence (p = 0.005) and well-demarcated borders (p = 0.031) were more frequently noted in BCCs < 5 mm than in bigger tumors. Lesions on the face showed clearly defined borders (p = 0.031) and interrupted follicle pattern (p < 0.001) more frequently than tumors located beyond the face. Nodular BCCs displayed interrupted follicle pattern (p = 0.001) and absence of pink-orange fluorescence (p < 0.001) more commonly than superficial subtypes. Non-pigmented BCCs more frequently showed lack of blue-green fluorescence (p = 0.007) and interrupted follicle pattern (p = 0.018) compared to pigmented variants. UVFD may be a valuable, complementary to PD, tool in the diagnosis of BCC, particularly in small tumors, lesions located on the face and nodular or non-pigmented subtypes.

Evaluation of confocal laser scanning microscopy in histological classification and photodynamic therapy of low-risk basal cell carcinoma.

Confocal laser scanning microscopy (CLSM) is a noninvasive technique utilized for identification and analysis of skin malignancies. Several studies have applied CLSM in monitoring the treatment of basal cell carcinoma (BCC). To investigate the diagnostic value of CLSM in low-risk BCC and the evaluation of photodynamic therapy (PDT). We diagnosed 149 patients with BCC using CLSM and histopathological examination. Based on histopathology, we summarized the classification of low-risk BCC along with imaging features observed through CLSM. Thirty-four patients with low-risk BCC underwent PDT treatment, and we used CLSM to evaluate its efficacy. Out of 149 BCCs examined by CLSM, 52 were diagnosed as the pigmented type, 87 as the nodular type and 10 as the superficial type. After histopathological examination of the 52 BCCs identified as pigmented by CLSM, 44 out of 52 were seen to be pigmented, 5 were nodular and 3 were superficial. The histopathology results were consistent with CLSM for the 87 nodular and 10 superficial BCCs. The distinguishing CLSM feature of nodular BCC was tissue fissures around the tumour, while the pigmented mass was the CLSM characteristic of the pigmented type. The simultaneous occurrence of inflammation and increased vasculature was characteristic of superficial BCC. The effective rate of PDT was 100%, and the cure rate was 68%. At the 12-month follow-up, the recurrence rate of PDT was 12%; 15% for nodular BCC, 10% for pigmented and 0% for superficial. The tissue classification of CLSM for low-risk BCC was consistent with histopathology. CLSM can be used to monitor the -efficacy of PDT for low-risk BCC.

Predictors of Local Invasion in Infiltrative Basal Cell Carcinoma: Tumour Budding Outperforms the WHO Subtyping.

Tumour budding (TB) correlates with increased local invasion in various neoplasms. Certain basal cell carcinomas (BCCs) exhibit local aggressiveness. Detecting adverse prognostic factors in partial biopsies could aid in identifying cases with heightened local risk. The absolute number of TB (≤ 3 tumour cells) in excision specimens of 271 infiltrative BCCs (0: absent; 1: 1-2 foci; 2: ≥ 3 foci; 3: ≥ 10 foci), the histopathological subtype and depth of infiltration, perineural invasion, and other histological features were evaluated. A significant correlation was found between TB and both depth of infiltration (rho 0.445, p < 0.001) and perineural invasion (p = 0.009). In the multivariate analysis of depth and perineural invasion (multiple regression, stepwise), TB was identified as a significant covariate together with diameter, inflammation, and perineural invasion for the former, and depth for the latter. Conversely, no correlation existed between the WHO histological subtypes (infiltrating, sclerosing, and micronodular), and depth of infiltration or perineural invasion. This study demonstrates the value of TB as a biomarker for local invasiveness in BCC. In routine practice, a count of ≥ 3 TB foci in lesions incompletely excised or with narrow tumour-free surgical margins would be a straightforward and reproducible method to guide BCC treatment.

Basocellular carcinoma of atypical location

Basal cell carcinoma is the most common malignant cutaneous tumor in humans. It can occur in any area of the body surface, but predominates in photo-exposed areas, particularly the face and trunk.

Advanced and Metastatic Non-Melanoma Skin Cancer: Epidemiology, Risk Factors, Clinical Features, and Treatment Options.

Non-melanoma skin cancers (NMSC) form the majority of skin cancers, with basal cell carcinoma (BCC) being the most common and cutaneous squamous cell carcinoma (cSCC) being second. Prolonged ultraviolet (UV) exposure, aging, male gender, and immunosuppression represent most of the causes of this category of diseases. BCCs and cSCCs both include different types of skin cancers, such as nodular or morpheaform BCC or flat cSCC. Locally advanced and metastatic NMSCs cannot be treated surgically; thus, systemic therapy (TKI and Immunotherapy) is needed. Interestingly, NMSCs are frequently linked to abnormal Hedgehog (HH) signaling which most systemic immunotherapies for these cancers are based upon. Of note, the first line therapies of BCC, sonidegib and vismodegib, are HH inhibitors. Programmed death receptor 1 antibody (PD-1) inhibitors such as cemiplimab, pembrolizumab, and nivolumab have been approved for the treatment of cSCC. Thus, this paper reviews the epidemiology, risk factors, clinical features, and treatment options for both BCC and cSCC.

Clinico-epidemiological characteristics and long-term surgical outcome of basal cell carcinoma treated with standard excision in patients of skin of colour: A retrospective study from Northern India.

Background There is scant data on basal cell carcinoma (BCC) in Indian patients. This retrospective study was conducted to explore epidemiology, risk factors, clinical and pathological aspects, and long-term treatment outcomes of BCC in a cohort of North Indian patients. Methods Data about patients registered in the dermatosurgery clinic between 01 January 2017 and 31 December 2022 with a confirmed diagnosis of BCC was collected. Results Among the 83 patients, 56.6% were females, and the median age was 62 years (6-85 years). Most patients (81.9%) had a single BCC lesion, resulting in a total of 126 assessed lesions. The median size of BCC at presentation was 1.90 cm, with nodular BCC being the most common histopathological subtype (39.7%). Head and neck region involvement was observed in 82.5% of patients, with the malar region, nose, and periorbital region being the most commonly affected sites. Pigmentation was clinically evident in 45.2% of cases. Surgical excision was the primary treatment modality (71.1% of patients). The median follow-up duration was 40 months (6-57 months). Recurrence occurred in five patients, with a longer disease-free survival period observed in the surgically treated group (55.58 ± 0.98 months) compared to patients treated with medical or destructive therapies (43.6 ± 3.482 months) (p = 0.003). Conclusion The data from this hospital-based study indicated a slight predilection for females among North Indian patients with BCC, with most cases occurring during their seventh decade of life. The condition commonly occurred on sun-exposed areas such as the malar region and nose, with a high percentage of pigmented lesions. Recurrence following surgical excision was rare, and overall treatment outcomes were favourable.

Incidence and geographic differences in keratinocyte carcinoma and Bowen's disease in office‐based dermatological practice between 2013 and 2022: A nationwide Danish registry‐based study

AbstractBackgroundRates of keratinocyte carcinoma (KC) across Europe are impacted by population demographics and geography. Regional differences in KC occurrence exist, but few European studies investigate incidences of specific subtypes in the secondary healthcare sector on a national level.ObjectivesTo determine geographical differences in incidence rate and lifetime risk of KC subtypes across Denmark, including nodular and superficial basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and the KC precursor, Bowen's disease (BD), identified in office‐based dermatological practice.MethodsBased on a nationwide registry (The Danish Skin Cancer Registry), all patients in Denmark's five regions with a histologically‐ or clinically verified KC or BD registered in a state‐funded office‐based dermatology practice between 2013 and 2022 were included. Trends in national‐ and region‐specific age and sex standardised tumour incidence rates (STIR) were calculated. Further, national lifetime risk of each tumour subtype was estimated.ResultsBetween 2013 and 2022, the combined STIR for KC/BD rose 172% nationally from 180 to 489 per 100,000 person‐years (PY). This increase reflected rising rates of nodular BCC, SCC, and BD, while superficial BCC incidence was relatively stable. Regional differences in STIR for combined KC/BD were observed, with the Capital Region and North Jutland generally demonstrating higher rates than Zealand, Southern‐ and Central Denmark (e.g., North Jutland vs. Southern Denmark: 714 vs. 405/100,000PY). While the estimated lifetime risk of developing at least one KC or BD tumour was 21.8%, risk varied with tumour subtype, resulting in subtype‐specific risks of 16.4%, 5.1%, 1.9% and 1.3% for nodular BCC, superficial BCC, SCC, and BD, respectively.ConclusionsIn Denmark's secondary dermatological care sector, incidence of nodular BCC, SCC and BD continues to rise with an overall lifetime risk nearing 22%. While KC incidence is increasing in Denmark, the study detected differences in geographical trends and rate increases of specific tumour subtypes.

Excision of basocellular carcinoma in the face with the rieger flap and A-T flap methods: a narrative review

Excision of basocellular carcinoma in the face with the rieger flap and A-T flap methods: a narrative review

Jet-injection assisted photodynamic therapy for superficial and nodular basal cell carcinoma: A pilot study.

Photodynamic therapy (PDT) with topical δ-Aminolevulinic acid (ALA) has efficacy in treating basal cell carcinoma (BCC) but is limited by incomplete penetration of ALA into the deeper dermis. This prospective open-label pilot trial investigated the safety and efficacy of photosensitizer jet injection for PDT (JI-PDT) for BCC treatment. It was performed with 15 patients (n = 15) with histologically confirmed, untreated, low-risk nodular BCCs at a single institution. For the intervention, JI-PDT patients (n = 11) received two sessions of jet-injected ALA with PDT separated by four to 6 weeks. To further understand treatment technique, another group of patients (n = 4) received jet-injected ALA followed by tumor excision and fluorescence microscopy (JI-E). Treatment tolerability was assessed by local skin responses (LSR) score at five distinct time intervals. Fluorescence microscopy assessed protoporphyrin IX penetration depth and biodistribution within the tumor. At the primary endpoint, tumor clearance was evaluated via visual inspection, dermoscopy and reflectance confocal microscopy. Postinjection and postillumination pain levels, and patient satisfaction, were scored on a 0-10 scale. Fifteen participants with mean age of 58.3, who were 15/15 White, non-Hispanic enrolled. The median composite LSR score immediately after JI-PDT was 5(interquartile range [IQR] = 3) which decreased to 0.5 (IQR = 1) at primary endpoint (p < 0.01). Immunofluorescence of excised BCC tumors with jet-injected ALA showed photosensitizer penetration into papillary and reticular dermis. Of the 13 JI-PDT tumors, 11 had tumor clearance confirmed, 1 recurred, and 1 was lost to follow-up. 1/11 patients experienced a serious adverse event of cellulitis. 70% of patients had local scarring at 3 months. Patients reported an average pain level of 5.6 (standard deviation [SD] = 2.3) during jet injection and 3.7 (SD = 1.8) during light illumination. Jet injection of ALA for PDT treatment of nodular low-risk BCC is tolerable and feasible and may represent a novel modality to improve PDT.