Invasive Basal Cell Carcinoma Research Articles

Basal Cell Carcinoma of the Head With Intense [68Ga]OncoFAP Uptake.

A 72-year-old man with advanced locally invasive basal cell carcinoma of the forehead failed several pretreatments including surgery and radiation. MRI was not feasible because of the presence of facial implants. CT scan did not provide clear evidence of vital/avital tumor sites as a result of slow progression and previous radiation treatments. Due to limited treatment options, the patient underwent evaluation with 68Ga-OncoFAP PET/CT for potential stereotactic body radiation therapy. We present a rare case of advanced and metastasized basal cell carcinoma with vigorous FAP (fibroblast activation protein) expression.

COL10A1 expression distinguishes a subset of cancer-associated fibroblasts present in the stroma of high-risk basal cell carcinoma.

Basal cell carcinoma (BCC) is the most frequently diagnosed skin cancer and the most common malignancy in humans. Different morphological subtypes of BCC are associated with a low or high risk of recurrence and aggressiveness, but the underlying biology of how the individual subtypes arise remains largely unknown. As the majority of BCCs appear to arise from mutations in the same pathway, we hypothesized that BCC development, growth and invasive potential is also influenced by the tumour microenvironment and, in particular, by cancer-associated fibroblasts (CAFs) and the factors they secrete. To characterize the stroma of the different BCC subtypes with a focus on CAF populations. To investigate the stromal features of the different BCC subtypes, we used laser capture microdissection (LCM) followed by RNA sequencing (RNA-Seq). Fifteen BCC samples from five different 'pure' subtypes (i.e. superficial, nodular, micronodular, sclerosing and basosquamous; n = 3 each) were selected and included in the analysis. Healthy skin was used as a control (n = 6). The results were confirmed by immunohistochemistry (IHC). We validated our findings in two independent public single-cell RNA-Seq (scRNA-Seq) datasets and by RNAscope. The stroma of the different BCC subtypes were found to have distinct gene expression signatures. Nodular and micronodular appeared to have the most similar signatures, while superficial and sclerosing the most different. By comparing low- and high-risk BCC subtypes, we found that COL10A1 is overexpressed in the stroma of sclerosing/infiltrative and basosquamous but not in micronodular high-risk subtypes. Those findings were confirmed by IHC in 93 different BCC and 13 healthy skin samples. Moreover, scRNA-Seq analysis of BCCs from two independent datasets found that the COL10A1-expressing population of cells is associated with the stroma adjacent to infiltrative BCC and shows extracellular matrix remodelling features. We identified COL10A1 as a marker of high-risk BCC, in particular of the sclerosing/infiltrative and basosquamous subtypes. We demonstrated at the single-cell level that COL10A1 is expressed by a specific CAF population associated with the stroma of infiltrative BCC. This opens up new, tailored treatment options, and suggests COL10A1 as a new prognostic biomarker for BCC progression.

MicroRNA Signatures Associated with Basal Cell Carcinoma Subtypes

Basal cell carcinoma (BCC) is classified histologically into subtypes that determine treatment decisions. Micro RNAs (miRs) are short non-coding RNAs that may serve as diagnostic biomarkers. We investigated if particular miRs could distinguish BCC subtypes. We sequenced miRs from 55 archival BCC and 9 control skin specimens, and then validated these miRs by qRT-PCR assay on a second BCC cohort (18 superficial, 16 nodular, 15 infiltrative) and control skin (n= 12). Expression values for individual miRs were normalized to miR-16-5p, which was least variant among the control skin and BCC samples. We found that 1) miR-383-5p and miR-145-5p are downregulated in all BCC subtypes compared to control skin, 2) miR-181c-5p is downregulated in superficial compared to invasive (nodular/infiltrative) BCC, and 3) miR-22-5p and miR-708-5p are upregulated in infiltrative compared to superficial/nodular BCC and miR-30c-5p is downregulated in infiltrative compared to nodular BCC. Receiver operating characteristic analysis demonstrated excellent capacity of these miRs to discriminate between BCC and control skin (area under curve 0.94-0.98), while capacity to discriminate between superficial and invasive subtypes was less robust (area under curves 0.7-0.8). Future prospective studies may determine the utility of these miRs as diagnostic biomarkers to guide biopsy and treatment of BCC.

Хирургическое лечение базалиомы внутреннего угла глазной щели с закрытием дефекта свободным лоскутом. Клинический случай

Basal cell carcinoma is a tumor of the basal layer of the skin epithelium. It occupies an intermediate position between benign and malignant tumors. It develops from atypical basal cells of the epidermis and follicular epithelium. It does not metastasize. The occurrence on the lower eyelid is about 65 %, on the medial canthus about 15 %, on the upper eyelid about 15 % and on the lateral canthus 5 % of cases. Usually the neoplasm is painless, but more invasive basal cell carcinomas with perineural germination into the tissues of the eyelid and orbit can cause pain [1, 3]. The choice method of treatment of this disease is surgical. The operation is performed under a microscope, which allows to remove the altered tissues as much as possible and correctly match the edges of the donor material. To replace the surgical defect, a type of plastic was chosen: plastic with local tissues, free skin plastic. The skin flap was taken from the upper eyelid of the fellow eye [2]. There are several types of basal cell carcinomas: nodular, flat, and superficial. The nodular form is most common. A distinctive feature in most cases is pearl shade and waxy or translucent consistency of the tumor, more noticeable on the raised edges of the neoplasm. A characteristic and important symptom is telangiectasis marked at the edges of the neoplasm [1]. Initially, a painless nodule appears on the skin gradually, the nodule spreads over the area, accompanied by formation of ulcers, due to disturbance of blood supply and turns into ulcerative-nodular form. Ulceration can bleed. Further, basal cell carcinoma turns into a flat plaque with a peeling surface, a node protruding above the surface of the skin, or into a deep ulcer that destroys the underlying tissues. With advanced forms or inadequate treatment, the tumor can grow into the lacrimal pathways, the orbit and occasionally into the cranial cavity. The sprouting of orbital tumor causes diplopia and dislocation of the eyeball. Spontaneous regression is rare [3]. There are the following types of treatment: radiation, surgical, combined, medicinal, cryogenic, laser [4, 5]. Radiation, laser, cryogenic methods of treatment are carried out in a specialized cancer center. The surgical method is based on excision within healthy tissues with the least traumatization or destruction of surrounding tissues. Excision of a part of the eyelid weakens its horizontal tension; this circumstance requires special restorative techniques to prevent scarring. The choice method of the defect closure is the method of lateral displacement, plastic with a free flap or pedicle flap [4, 5]. Key words: basal cell carcinoma; surgery of basal cell carcinoma; plastic surgery with a free flap.

Significance of Basal Cell Carcinomas Exhibiting Intravascular Invasion.

Intravascular invasion of tumor cells can be associated with metastasis in many cancers. Basal cell carcinomas (BCCs), however, rarely metastasize; therefore, the clinical impact of intravascularly invasive BCC (IVBCC) is currently unclear. Because of these facts and the rarity of IVBCC, questions have arisen on whether IVBCC truly exists. We present 4 cases of IVBCC: one case with obvious tumor islands within immunolabeled blood vessels in the context of advanced disease and 3 cases found incidentally during Mohs micrographic surgery. We discuss the difficulty in studying IVBCC, the idea that it could be due to artifact, and the lack of direct clinical-pathological correlation. Given these challenges, we propose diagnostic criteria for IVBCC to decrease ambiguity for pathological diagnosis. Such criteria may facilitate further studies on the clinical significance of IVBCC.

A Survey on Orbital Space-Occupying Lesions during a Twelve-Year Period from a Referral Center in Iran.

In this study, we describe different orbital space-occupying lesions (SOLs) from a referral center in Iran. In this retrospective case series, all records of "orbital tumors" with a definite histopathologic diagnosis at a referral center in Iran were reviewed from April 2008 to May 2020. A total of 375 orbital SOLs were included. The study population consisted of 212 (56.5%) female and 163 (43.5%) male subjects with overall mean age of 31.09 21.80 years. The most common clinical presentation was proptosis and the superotemporal quadrant was the most frequent site of involvement. Extraconal lesions (276 cases, 73.6%) outnumbered intraconal lesions (99 cases 26.4%). The great majority of SOLs (344, 91.7%) were primary, while 24 (6.4%) were secondary and 7 (1.9%) were metastatic. Benign lesions (309, 82.4%) were much more common than malignant SOLs (66, 17.6%). Overall, dermoid cysts and malignant lymphoma were the most prevalent benign and malignant orbital SOLs, respectively. The malignant to benign lesion ratio was 0.46 in children (18 years), 0.81 in middle-aged subjects (19-59 years), and 5.9 in older (60 years) cases. The most common type of malignancy was rhabdomyosarcoma in children, lymphoma in middle-aged subjects, and invasive basal cell carcinoma in older age group. Over the 12-year study period, benign, primary, extraconal orbital SOLs were more frequent than malignant, secondary, and intraconal lesions. The ratio of malignant lesions increased with age in this cohort of patients.

Recurrence Following Globe Sparing Excision for Basal Cell Carcinoma with Anterior Orbital Invasion.

Globe-sparing excision for periocular basal cell carcinoma (BCC) with orbital invasion has evident benefits, but the ensuing morbidity and characteristics of recurrence are not well elucidated. This study aims to describe the extent of visual morbidity following globe-sparing excision, and the clinicoradiological characteristics of tumor recurrence. Multicentre retrospective case series. Eight patients were identified for inclusion in this series. Time to recurrence following globe-sparing excision ranged from 3 to 12 years. Seven patients (87.5%) presented with recurrent disease originating from the medial canthus. Clinical features at presentation included contracture ( n =4, 50.0%), upper lid ptosis ( n =3, 37.5%), a palpable mass ( n =2, 25.0%), and hypoesthesia ( n =2, 25.0%). Radiologically, tumor recurrence was predominantly characterized by isointense signals on T1 and T2-weighted sequences ( n =5, 62.5%) with moderate contrast enhancement. The most common histologic subtype in recurrent tumors was a mixed nodular and infiltrative growth pattern ( n =5, 62.5%). Perineural invasion was a feature in four (50%) cases. Salvage therapy in the form of exenteration was performed in seven cases. Vismodegib and adjuvant radiotherapy were provided for one case with surgically unresectable tumor recurrence. Globe-sparing excision for invasive periocular BCC can be complicated by late recurrence that develops rapidly despite silent neuroimaging for years. Early clinical signs are subtle. High-risk features predictive of recurrence include medial canthus location, mixed histological subtypes, and perineural invasion. Patients with such characteristics require lifelong clinical and imaging surveillance following globe-sparing excision.

Comparison of various clinicopathological parameters with a depth of invasion in basal cell carcinoma

Comparison of various clinicopathological parameters with a depth of invasion in basal cell carcinoma

Basal Cell Carcinoma of the Prostate: Case Reports Including an Unusual Presentation

Basal cell carcinoma of the prostate is a rare tumor subtype arising from the prostatic basal cells and follows a variable clinical course. We describe two cases of patients with basal cell carcinoma of the prostate treated at our center. One case involves a patient with prior radiation with brachytherapy for prostatic adenocarcinoma, who subsequently developed a locally aggressive and invasive basal cell carcinoma of the prostate that eventually required pelvic exenteration. To our knowledge, we are the first to describe a case of basal cell carcinoma of the prostate in a patient with prior radiation with brachytherapy for prostatic adenocarcinoma.

Treatment of basal cell carcinoma: An overview

Basal cell carcinoma (BCC) is the most common cutaneous cancer worldwide, but accounts for only 2–4% of skin cancers in Asian population. Tumor characteristics such as size, location, pathology, and risk of recurrence, as well as treatment tolerability, cost, and patient preference influence the selection of treatment. The goal of treatment is complete tumor removal in superficial/locally invasive BCCs and prolongation of survival in the rare setting of metastatic BCC. Various treatment options available include conventional surgical excision, Mohs micrographic surgery, cryosurgery, electrodesiccation and curettage, topical application of imiquimod or 5-fluorouracil, and photodynamic, and radiotherapy. Surgical excision and Mohs surgery are preferred because of low recurrence rate and the possibility to evaluate the clearance through histology. In the treatment of metastatic or locally advanced lesions, hedgehog pathway inhibitors and the recently approved drug cemiplimab can be beneficial. Sun protection and regular skin self-checks are recommended for all patients with BCC. This literature review gives an overview of the treatment of BCC.

(PO-091) Decision-Making Capacity in a Patient with Frontal Anosodiaphoria in the setting of Invasive Basal Cell Carcinoma

(PO-091) Decision-Making Capacity in a Patient with Frontal Anosodiaphoria in the setting of Invasive Basal Cell Carcinoma

Corneal Invasion by Basal Cell Carcinoma.

CASE PRESENTATION A 68-year-old man suffered with a basal cell carcinoma of the right lower eyelid, with features of the morpheaform and nodular types, treated by report with clear margins on Mohs resection and primary closure. Nine years later, an invasive recurrence involved the lateral canthus and lacrimal gland, producing restrictive strabismus. There was no radiographic evidence of orbital invasion. A Mohs resection, clearing the skin and conjunctiva, resulted in an 80% upper and 90% lower eyelid defect, exposing the anterior zygoma and the lateral 180° conjunctival defect (Fig. 1A). However, the region of the lacrimal gland was not cleared by Mohs surgery, and at the time of reconstruction, an intraoperative frozen section of the lacrimal gland demonstrated myoepithelial cells concerning for malignancy, prompting complete resection of the gland. The surrounding orbital fat and soft tissue were histologically clear of tumor. The lower eyelid was reconstructed with a hard palate graft and a myocutaneous advancement cheek flap anchored to the orbital rim. The upper eyelid was reconstructed with advancement of the remnant levator aponeurosis, Müller muscle, and conjunctiva, surfaced with a postauricular skin graft. Postoperatively, a PROSE lens (BostonSight, Boston, MA) was employed to maintain corneal integrity. One year later, the patient developed a second recurrence, treated with vismodegib, which produced clinical and radiographic tumor control but drug intolerance prompted its discontinuation. Eight months later, a third recurrence required re-excision of the tumor, which involved the lateral conjunctiva and extended to the anterior orbit. The area was repaired with a buccal mucosal graft. Globe preservation precluded achieving tumor-free margins. Postoperatively, the patient received 6 cycles of cemiplimab, which failed to suspend tumor progression. He was subsequently treated with sonidegib for a total of 11 months, which also failed to control the tumor, producing a palpable mass in the lower lid, cicatricial ectropion, and an adduction deficit (Fig. 1B). Neuroimaging demonstrated soft-tissue hyperintensity indicative of persistent tumor of the eyelid (lateral canthal infiltration indicated by the arrow) also involving the globe (Fig. 1C). The patient ultimately underwent orbital exenteration. Final pathology revealed invasive basal cell carcinoma, with corneal infiltration (Fig. 1D, E).FIG. 1.: Mohs resection of the initial recurrence of basal cell carcinoma resulted in an 80% upper eyelid defect and 90% lower eyelid defect (A). Following subsequent recurrences and prior to exenteration, a palpable mass was evident in the lower eyelid causing a cicatricial ectropion (B). Neuroimaging revealed lateral canthal infiltration of tumor, as indicated by the arrow (C). Histopathology of the exenteration specimen demonstrated basal cell carcinoma invading the corneal surface (hematoxylin and eosin stain 60× and 600×) (D, E).

Value of High-Frequency Ultrasound for Differentiating Invasive Basal Cell Carcinoma from Non-invasive Types

The purpose of the study was to evaluate the value of high-frequency ultrasound (HFUS) for differentiating invasive basal cell carcinomas (BCCs) from non-invasive BCCs. We established a prediction model based on ultrasound features and validated it further. One hundred patients in the pilot cohort and another 43 in the validation cohort were evaluated. All patients underwent HFUS examinations by the same radiologist, and then were divided on the basis of pathology into invasive and non-invasive types. With respect to growth pattern, 60.5% of invasive BCCs had an irregular pattern, whereas 89.5% of non-invasive BCCs had a nodular or crawling pattern (p < 0.001). As for the layers involved, the more invasive BCCs broke through the dermis compared with non-invasive BCCs (23.3% vs. 1.8%) (p < 0.001). With respect to intralesional hyperechoic spot distribution, invasive and non-invasive BCCs tended to be clustered and absent/scattered-like, respectively (55.8% vs. 91.2%) (p < 0.001). On the basis of the aforementioned features, a prediction model was established with accuracies of 84.0% and 76.7%, respectively, in the pilot and validation cohorts. HFUS holds promise for the differentiation of the invasiveness of BCCs and is helpful in its clinical management.

Basal Cell Carcinoma Destruction by a Concentrate of Proteolytic Enzymes Enriched in Bromelain: A Preliminary Report

Objectives: Basal Cell Carcinoma (BCC) is the most common skin cancer generally treated by a variety of surgical and non-surgical destructive therapies. A Concentrate of Proteolytic Enzymes Enriched in Bromelain (CPEEB) derived from the stems of pineapples is approved for use for debriding deep burns. Prior studies suggest that bromelain also has anti-tumor effects. We describe our preliminary off-label treatment experience using topical CPEEB for the destruction of six BCCs in three patients. Methods: CPEEB was self-applied by three patients on six different Morphea, nodular, and superficially invasive BCCs. The CPEEB was applied as a thin layer prior to bedtime and left for a period of 9-12 hours. The wound was then covered with a petrolatum-based ointment for the next 24 hours. Application of the CPEEB was repeated up to 5 times over the course of 10 days, during which the patients were monitored daily and reevaluated by a board-certified plastic surgeon. If necessary, the CPEEB was reapplied up to five additional times over the next 10-day period. If necessary, any remaining lesion was surgically excised (MOHS surgery). The patients were then followed for up to 1 year. Results: Six BCCs located on the face, neck, and extremities were self-treated by three patients with 2-6 CPEEB applications. All of the BCCs were completely removed after the CPEEB application. CPEEB application was associated with local irritation and mild itching pain which resolved untreated within hours. In one patient, two of the lesion’s sites were surgically excised after 6 months with no tumor cells noted on histopathology. None of the BCCs recurred over the next 1 year. Conclusion: Our preliminary findings are a proof-of-concept that a concentrate of proteolytic enzymes enriched in bromelain may be a safe and effective destructive treatment for basal cell carcinomas. Future studies on larger groups of BCC patients are necessary in order to elucidate the potential use of CPEEB for this indication.

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.

Medial Canthal Contraction as a Marker for Orbital Invasion in Basal Cell Carcinoma.

Medial Canthal Contraction as a Marker for Orbital Invasion in Basal Cell Carcinoma.

Invasive basal cell carcinoma of the umbilical stalk.

Invasive basal cell carcinoma of the umbilical stalk.

S2498 Vismodegib, a Hedgehog Pathway Inhibitor, Causing Severe Liver Injury

INTRODUCTION: Vismodegib, a hedgehog pathway inhibitor used to treat locally advanced and metastatic basal cell carcinoma, can lead to severe hepatotoxicity. Patients who develop nausea, loss of appetite, and dysgeusia should have liver enzymes evaluated. Early detection of liver insult could lead to early discontinuation of the drug to prevent worsening liver injury, further workup and unnecessary hospitalization. CASE DESCRIPTION/METHODS: A 53 year old female with invasive basal cell carcinoma on vismodegib, presented with loss of appetite, RUQ abdominal pain and jaundice. Labs revealed a total bilirubin of 7.4 mg/dL, alkaline phosphatase 545 IU/L, AST 163 IU/L, and ALT 471 IU/L. Viral hepatitis and autoimmune panel was unremarkable. MRCP and an endoscopic ultrasound did not show any biliary obstruction. However, the biliary ducts appeared unusually small. Her bilirubin continued to increase, and the idea of vismodegib causing cholestatic liver injury and vanishing bile duct syndrome was entertained. However, ERCP revealed a normal cholangiogram. Liver biopsy was pursued and showed marked zone 3 canalicula cholestasis and marked duct injury in portal tracts suggesting vismodegib causing cholestatic liver injury. DISCUSSION: There have been a few cases now reporting vismodegib-induced liver injury. Luckily our patient slowly improved with drug withdrawal. However, there has been life-threatening hepatotoxicity and even death, especially in patients taking drugs with potential hepatotoxic effects. Liver enzymes can mimic the pattern of acute viral or autoimmune hepatitis or ischemic liver injury. Our initial suspicion given our patient's MRCP and EUS findings, with bile ducts appearing abnormally small, was drug-induced vanishing bile duct syndrome. Vanishing bile duct syndrome in adults is typically caused by autoimmune diseases, neoplasms such as Hodgkin’s lymphoma, infections such as CMV and drugs such as allopurinol. The diagnosis is made through liver biopsy containing at least 10 portal tracts, showing loss of interlobular bile ducts in > 50% of the portal tracts. Clinically, patients will have fatigue, weight loss, loss of appetite, and abdominal pain as a result of intrahepatic cholestasis. Treatment includes discontinuation of offending drug but others have trialed ursodiol. Our patient’s liver biopsy did not suggest this rare syndrome but we suspect that if she had continued vismodegib, her outcome could have been worse and her liver biopsy could have progressed to vanishing bile duct syndrome.Figure 1.: Magnetic resonance cholangiopancreatography did not show any evidence of obstruction. Biliary ducts appeared small.Figure 2.: Endoscopic retrograde cholangiopancreatography was unremarkable, without evidence of obstruction.

Eyelid skin trichilemmoma and underlying local malignancy: is an aggressive treatment necessary?

ObjectiveTrichilemmoma is a benign tumour derived from the outer root sheath of hair follicles. Trichilemmoma can be associated with basal cell carcinoma (BCC), either as a collision lesion or from...

CD73 Is Enriched in Cutaneous Carcinomas That Invade the Orbit.

To compare the expression of CD73 in indolent nodular basal cell carcinomas and cutaneous lesions that invade the orbit. Immunohistochemical staining for CD73 was performed on nodular basal cell carcinomas and invasive basal cell carcinomas. The numbers of positively staining cells were counted across 5 consecutive ×40 microscopic fields, and a statistical comparison was performed via a dedicated computerized software package. Ten control specimens and 11 invasive tumors were analyzed. In nodular basal cell carcinomas, the mean number of positively staining cells was 0.72/×40 field (standard deviation = 0.80 cells/×40 field), whereas invasive tumors demonstrated a mean of 6.53 positive staining cells/×40 field (standard deviation = 3.33 cells/×40 field). This difference was statistically significant (p = 0.0002). CD73 is enriched in orbital invasion of cutaneous carcinomas. This checkpoint may represent an important target for therapeutic management of these lesions. Immunotherapeutic agents that have been designed to treat other neoplasms may decrease the requirement for orbital exenteration in this clinical scenario.