Sanguinaria canadensis, also known as bloodroot, is a traditional medicine used by Native Americans to treat a diverse range of clinical conditions. The plants rhizome contains several alkaloids that individually target multiple molecular processes. These bioactive compounds, mechanistically correlate with the plant’s history of ethnobotanical use. Despite their identification over 50 years ago, the alkaloids of S. canadensis have not been developed into successful therapeutic agents. Instead, they have been associated with clinical toxicities ranging from mouthwash induced leukoplakia to cancer salve necrosis and treatment failure. This review explores the historical use of S. canadensis, the molecular actions of the benzophenanthridine and protopin alkaloids it contains, and explores natural alkaloid variation as a possible rationale for the inconsistent efficacy and toxicities encountered by S. canadensis therapies. Current veterinary and medicinal uses of the plant are studied with an assessment of obstacles to the pharmaceutical development of S. canadensis alkaloid based therapeutics.

Background: Cutaneous horns usually develop on a keratinocytic base with the histopathology on a spectrum ranging from benign keratosis through to invasive squamous cell carcinoma (SCC). Some features of horns are easily identified using dermatoscopy. Objective: To investigate if specific clinical or dermatoscopy features of horns correlate with the histopathology in the base of the horn. Methods: Consecutive horn cases (n=163) were assessed prospectively in vivo for horn height, terrace morphology and base erythema using a Heine Delta 20 dermatoscope. Cases with potentially confounding influences were excluded. A history of horn pain or pain on palpation was also recorded. Results: Benign keratosis (n = 49), actinic keratosis (n = 21), SCC in situ (n = 37) and invasive SCC (n = 56) were recorded. An invasive SCC presenting as a horn as most likely to have a height less than the base diameter, 66% (37/56). Compared to the other study entities, invasive SCC tends to have less terrace morphology (P<0.05), a higher incidence of base erythema (P<0.05) and more pain (P<0.01). Limitations: Data categories did not include anatomic site or horn growth rates. Excision selection bias favored the incidence of invasive SCC. Conclusions: Horns presenting on an invasive SCC base are more likely to have a height less than the diameter of the base, not to have terrace morphology, to have an erythematous base and to be painful.

Background: The depth of invasion by basal cell carcinoma (BCC) subtypes varies. Objective: To investigate BCC invasion depth variation by subtype and anatomic site. Method: A prospective consecutive case series of excised BCC from 2009 to 2014 in a single Australian clinic. Results: Descending mean depths for a total of 4,565 BCC cases by subtype were as follows: nodulocystic, 1.9 mm (n = 84, 95% CI: 1.70–2.03, P = 0.66); nodular, 1.6 mm (n = 947, 95% CI: 1.53–1.63, P < 0.0001); aggressive, 1.5 mm (n = 925, 95% CI: 1.44–1.59, P < 0.0001); superficial combined with nodular, 0.9 mm (n = 1,081, 95% CI: 0.83-0.90, P < 0.0001); and superficial, 0.3 mm (n = 1,528, 95% CI: 0.32-0.36, P < 0.0001). Deeper invasion was associated with increased chronic sunlight exposed sites. The deepest aggressive BCCs occurred on the neck with a mean depth of 1.8 mm (n = 46, 95% CI:1.47–2.21). Conclusion: We found significant differences in the depth of invasion for BCCs by sex, subtype, and anatomic site. For BCC with characteristics matching this study, overall adequate microscopic excision depths are proposed: superficial, 1.0 mm; superficial combined with nodular, 2.0 mm; nodular, 3.0 mm; and aggressive, 3.0 mm.

Compare the dermatoscopy vascular features of well differentiated with non-well differentiated squamous cell carcinoma (SCC). A prospective study of 294 consecutive cases of histopathologically confirmed invasive SCC compared the dermatoscopic vascular features of well to combined moderate and poorly differentiated tumors. These features were recorded live directly from the patients and included: the percentage of pink in the tumor, the presence of branching, serpentine, dot, hairpin, glomerular and linear vessels, and the number of these vessel types present within each tumor. Vessel types were also reviewed by tumor depth in 1 mm increments. Two medical practices in Sydney, Australia. Eighty-six female and 208 male patients (29-95 years old). Dermatoscopic vascular feature variation between grades of tumor differentiation and tumor depth. Of 294 invasive SCCs, 255 (87%) were well differentiated, 32 (11%) were moderately differentiated and 7 (2%) were poorly differentiated. The percentage of pink areas within tumors varied between differentiation grades. The combined group of moderate and poorly differentiated tumors displayed more branching (28%, P<0.001) and serpentine (62%, P<0.005) blood vessels compared to well differentiated tumors (8% and 38%, respectively). Moderate and poorly differentiated tumors displayed larger numbers of vessel types (3.3) compared to well differentiated tumors (2.6, P < 0.01). Branching and serpentine vessels both increased in incidence with increasing tumor depth (p<0.05). Grades of tumor differentiation in SCC display varying dermatoscopic vascular features. The incidence of branching and serpentine vessels increases with increasing tumor depth and the shift towards poor differentiation.

Background: Infiltrating basal cell carcinoma (BCC) has associated features that may be readily identified using dermatoscopy. Objective: Investigate a stellate dermatoscopy pattern extending from the peripheral margin of infiltrating BCC. Methods: A total of 741 consecutive cases of BCC were assessed retrospectively using non-polarized dermatoscopy. Following histopathologic examination, cases were categorized into six different BCC subtypes. Infiltrating cases numbered 107. This stellate feature was defined as a geometric star shaped pattern extending outwards from the circumferential peripheral edge of the tumor, and identified by white lines, vessels or uneven skin surface morphology. The percentages of infiltrating subtype within the tumor mass and tumor depth were compared, with and without the stellate pattern. Results: Infiltrating BCC displayed the stellate pattern more than other BCC subtypes. Concordance between the two observers was almost perfect for white lines: Kappa coefficient of 0.87 (95% CI: 0.0.79-0.95) P<0.01 and substantial for vessels: Kappa coefficient of 0.71 95% CI: 0.59-0.84) P<0.01. Folds were only recorded in infiltrating cases (n=3). Compared to other BCC subtypes the stellate pattern had a sensitivity of 31.7% and specificity of 94.1%. A higher mean fraction of the tumor mass containing infiltrating subtype was found when comparing stellate pattern observed to stellate pattern not observed (P<0.01). No statistically significant association was found between the tumor depth with and without the stellate pattern. Conclusion: This study found a higher incidence of the stellate pattern within infiltrating BCC compared to the other BCC subtypes. As the percentage of the infiltrating subtype within the tumors increased the incidence of the stellate pattern also increased.