Basal cell carcinoma with perineural invasion: A prospective study examining subtype, tumor surface diameter, invasion depth, and anatomic site in 3005 consecutive cases.

BACKGROUND: Basal cell carcinoma (BCC) may present with or without perineural invasion (PNI). We reviewed BCC for PNI by subtype, microscopic tumor surface diameter, invasion depth, and anatomic site. METHOD: Consecutive excisions were prospectively collected in an Australian center 2016-2018. RESULTS: Total cases were 3005 including 40 with PNI: 28 in males, 12 in females. Superficial and nodular subtypes had no PNI. As the percentage tumor mass of infiltrative BCC increased beyond 90% the presence of PNI substantially escalated (OR7.0). Comparing PNI absent or present the respective maximum mean tumor microscopic surface diameters ranged from (95%CI [9.6-10.0] P < .001) to 11.2 mm (95%CI [9.4-13.0] P = .59). Respective maximum mean invasion depths were from 1.0 mm (95%CI [0.98-1.05] P < .001) to 2.3 mm (95%CI [1.8-2.7] P < .001). Respective maximum mean invasion depths were from 1.0 mm (95%CI [0.98-1.05] P < .001) to 2.3 mm (95%CI [1.8-2.7] P < .001) to 2.3 mm (95%CI[1.8-2.7] P < .001). Males recorded most PNI on the scalp, followed by cheek and chin. Patients with more than two BCC cases had a greater proportional PNI risk (OR3.7). Mean PNI nerve diameters were 0.06 mm2 (males) and 0.03 mm2 (females). CONCLUSION: Increases in percentage infiltrative subtype within the tumor mass, microscopic tumor diameter, tumor invasion depth, and BCC cases per patient all recorded more PNI. Minimum invasion depths with PNI were 1.0 mm on males (nose) and 1.0 mm females (forehead).

Early invasive squamous cell carcinoma recurrence rates: A study examining surgical margins, tumor surface diameter, invasion depth, and grade of differentiation in 1296 cases over 9 years.

BACKGROUND: Invasive squamous cell carcinoma (SCC) is typically treated by surgical excision. METHODS: Consecutive SCC excisions were reviewed prospectively in a single Australian center from 2009 to 2017. Cases were examined for recurrence by histopathologic margins, microscopic tumor surface diameter, invasion depth, grade of differentiation, and anatomic site. RESULTS: Over 9 years, 1296 cases were collected. By grade of differentiation maximum average microscopic surface diameters ranged from 8.0 to 9.6 mm and maximum average depths from 1.3 to 2.5 mm. Minimum average histopathologic margins for well, moderate, and poorly differentiated SCC, respectively, were 1.4, 1.1, and 1.3 mm. Recurrence occurred in 1.7% of well (n = 18/1084), 1.8% moderate (n = 3/165) and 6.4% in poorly differentiated (n = 3/47) SCC. No recurrence occurred beyond a histopathologic margin of 3.5 mm for well and 2.5 mm for moderately differentiated SCC. Highest recurrence for well-differentiated SCC by anatomic site was the lip (7.0%) then ear (4.6%). CONCLUSION: We found a recurrence rate of 1.0% for histopathologic margins of 1.5 mm with early well-differentiated SCC. The grade of differentiation and anatomic site had a larger influence on recurrence rates compared to the histopathologic margins. Poorly differentiated SCC and ear or lip sites require wider surgical margins.

Assessing the risk of epidemic dropsy from black salve use.

Epidemic dropsy is a potentially life-threatening condition resulting from the ingestion of argemone oil derived from the seeds of Argemone mexicana Linn. Exposure to argemone oil is usually inadvertent, arising from mustard cooking oil adulteration. Sanguinarine, an alkaloid present in argemone oil, has been postulated as a causative agent with the severity of epidemic dropsy correlating with plasma sanguinarine levels. Cases of epidemic dropsy have also been reported following the topical application of argemone containing massage oil. Black salve, a topical skin cancer therapy also contains sanguinarine, but at significantly higher concentrations than that reported for contaminated massage oil. Although not reported to date, a theoretical risk therefore exists of black salve inducing epidemic dropsy. This literature review explores the presentation and pathophysiology of epidemic dropsy and assesses the risk of it being induced by black salve.

Dermoscopy features of atypical fibroxanthoma: A multicenter study of the International Dermoscopy Society.

BACKGROUND/OBJECTIVES: Little is known about the dermoscopic features of atypical fibroxanthoma. METHODS: This was a case-control study. Atypical fibroxanthoma lesions were compared with a control group with non-melanoma skin cancer. RESULTS: Altogether 40 atypical fibroxanthoma were collected. Most developed in men (93%), appearing mainly as nodular (63%), amelanotic (93%) and ulcerated (78%) lesions. Most lesions were located on the scalp (55%) and the ears (13%). Dermoscopically, most atypical fibroxanthoma displayed red (83%) and white (70%) structureless areas and irregular linear vessels (43%). A series of features achieved statistical significance when comparing atypical fibroxanthoma with non-melanoma skin cancer. The presence of red and white structureless areas and white lines, and the absence of yellowish-white opaque scales, hairpin vessels and arborising vessels were predictive of atypical fibroxanthoma in univariate analysis. However, when squamous cell carcinoma was excluded from the analysis, none of the criteria achieved statistical significance. When basal cell carcinoma was excluded, three variables achieved statistical significance in predicting atypical fibroxanthoma: red, structureless areas, the absence of opaque yellowish-white scales and absence of white circles. CONCLUSIONS: Atypical fibroxanthomas seem to be barely distinguishable from basal cell carcinoma dermoscopically, but they are more easily distinguishable from a well to moderately differentiated squamous cell carcinoma. A histopathological examination is needed for the final diagnosis.

Superficial basal cell carcinoma: A comparison of superficial only subtype with superficial combined with other subtypes by age, sex and anatomic site in 3150 cases.

BACKGROUND: Basal cell carcinoma (BCC) may present as superficial subtype alone (sBCC) or superficial combined with other subtypes. The objective of this study was to compare sBCC without or with other BCC subtypes by age, sex and anatomic site. METHODS: We retrospectively collected superficial BCC with the above characteristics from an Australian center during 2009 to 2014. RESULTS: We recorded 1528 sBCC and 1622 superficial BCC combined with other BCC subtype cases. Males numbered 2007 and females 1140. On males, head sites (forehead, cheek, nose and ear combined) compared to limb plus trunk sites displayed a higher incidence of superficial BCC combined with either nodular and or aggressive BCC subtypes (OR 13.15 CI 95% 8.9-19.5 P < .0001). On females a similar comparison also found a higher incidence of superficial BCC combined with solid subtype BCC on head sites compared to trunk and limb sites (OR 9.66 CI 95% 5.8-16.1 P < .0001). CONCLUSION: Superficial BCC alone is more likely on younger females on trunk and limb sites. Small partial biopsies reported as sBCC may miss other BCC subtypes present with higher risk on facial sites for males and females. Males had smaller proportions of superficial only subtype BCC on facial and ear sites compared to females.

Invasive Squamous Cell Carcinoma: A Comparison of Tumors With or Without Horn Presentation Based on Age, Sex, Anatomic Site, Tumor Diameter, Depth of Invasion, and Grade of Differentiation in 1,666 Cases.

INTRODUCTION: Invasive squamous cell carcinoma (SCC) may present clinically with or without a horn. OBJECTIVE: To compare invasive SCC with or without horn presentation by anatomic site, tumor diameter, depth, and grade of differentiation. MATERIALS AND METHODS: The above characteristics of invasive SCC with or without horns were compared using a logistic regression model adjusted for potential confounders. RESULTS: There were 7.0% horns (n = 116) and 93.0% nonhorns (n = 1,550) in 1,666 cases. The median tumor diameter was 6 mm for horns, and 8 mm for nonhorn cases, p < .001. The median depth of invasion was 0.8 mm for horn cases and 1.3 mm for nonhorns, p < .001. Most cases were well-differentiated SCC for both horns (n = 102, 87.9%) and nonhorns (n = 1,265, 81.6%) p = .07. Horn cases had a borderline significant shift to well differentiation with moderate differentiation in 11.2% of cases (n = 13) and poor differentiation in 0.9% (n = 1). CONCLUSION: Horns presented on invasive SCC with reduced tumor diameters and reduced invasion depths compared to nonhorns. Horns presenting on invasive SCC were usually well differentiated. However, moderate and even poor differentiation can occur within a horn base.

Sanguinaria canadensis: Traditional Medicine, Phytochemical Composition, Biological Activities and Current Uses.

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.

The Hunt for Baby Melanomas: A Prospective Study of the Dermoscopy Features on 100 Small Melanoma Cases with in Vivo Surface Diameters up to a Maximum of 6 mm.

Introduction: Early diagnosis can improve melanoma prognosis. Dermoscopy can enhance early melanoma recognition. Objectives: Examine the dermoscopy features of early melanoma up to a maximum surface diameter of 6 mm. Methods: Consecutive melanoma cases were collected from two medical practices in Sydney, Australia 2019-2021. Dermoscopy features were recorded for melanomas by maximum surface diameter, to the nearest 0.1 mm, to a limit of 6 mm. Results: Total cases numbered 100; with males (N = 48) and females (N = 52), melanoma in situ (MIS, N = 96) and invasive (N = 4). The most frequent anatomic sites on both males and females were back (males N = 20, females N = 16) then knee or leg (males N = 8, females N = 12). Minimum respective MIS diameters for males/females was 1.2/2.0 mm and for invasive cases 2.0/3.4 mm. Highest frequency dermoscopy features were: light brown, dark brown, gray and asymmetric melanoma shape. Brown pigment in hair follicles were more frequent on legs compared to other anatomic sites (odds ratio [OR] 14.6; 95% CI 1.29-165.17, P 0.03). Pseudopods were substantially increased in frequency comparing diameters less than 4 mm with 4 up to 6 mm (OR 8.81; 95% CI 1.05-73.9, P 0.004). Structureless area cases recorded increased gray (OR 7.08; 95% CI 1.61-31.11, P=0.01). Melanomas with edge angulation were noted in 20%-50% of cases across diameters 1-6 mm, less frequent were pigmented circles and polygons. Conclusions: Watch out! MIS presented with a surface diameter of just 1.2 mm and invasive melanoma 2.5 mm. Pseudopods were a strong clue to melanomas with a surface diameter less than 5mm. We found melanomas on leg sites displayed more frequent pigmented hair follicles.

Early Squamous Cell Carcinoma With Perineural Invasion: A Prospective Study Examining Anatomic Site, Tumor Surface Diameter, Invasion Depth, and Grade of Differentiation in 1,772 Consecutive Cases.

BACKGROUND: Squamous cell carcinoma (SCC) may present with perineural invasion (PNI). OBJECTIVE: To investigate the characteristics of early invasive SCC with or without PNI. METHODS: Consecutive SCC excisions were prospectively reviewed from a single Australian community-based practice for 2016-2018. Tumor characteristics recorded were anatomic site, maximum microscopic tumor surface diameter, invasion depth, grade of differentiation, and diameter of nerves with PNI. RESULTS: In total, 1,772 cases were collected. No PNI cases were found on female patients. Seven of the total 10 PNI cases were on facial sites. Maximum average microscopic tumor surface diameters ranged from 10.1 mm (well differentiated) up to 11.0 mm (moderately differentiated). Maximum average invasion depths by differentiation ranged from 1.7 (well differentiated) up to 2.6 mm (poorly differentiated). The PNI cases were as follows: well differentiated (n = 0), moderately differentiated (n = 4), or poorly differentiated (n = 6). Minimum average histopathological margins for well, moderately, and poorly differentiated SCC, respectively, were 1.4, 1.1, and 1.3 mm. Minimum microscopic tumor surface diameters for PNI cases were 7 mm for moderately and 5 mm for poorly differentiated SCC. Minimum microscopic invasion depths for PNI cases were 2.2 mm for moderate and 0.9 mm for poor differentiation. CONCLUSIONS: We found early SCC with PNI displayed nerve diameters of 0.1 mm or less and were exclusively on male patients aged 60 or older, on chronically sun-exposed sites of the head and upper midline anterior chest. Histopathological features associated with PNI were moderate and poor differentiation, tumor invasion beyond 0.9 mm, and adjacent lymphocytosis.

Basal cell carcinoma: variation in invasion depth by subtype, sex, and anatomic site in 4,565 cases.

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.

A Review of Black Salve: Cancer Specificity, Cure, and Cosmesis.

Black salve is a topical escharotic used for the treatment of skin cancer. Although promoted as a safe and effective alternative to conventional management by its proponents, limited clinical research has been undertaken to assess its efficacy and potential toxicities. Patients are increasingly utilizing the Internet as a source of health information. As a minimally regulated space, the quality and accuracy of this information vary considerably. This review explores four health claims made by black salve vendors, investigating its natural therapy credentials, tumour specificity, and equivalence to orthodox medicine in relation to skin cancer cure rates and cosmesis. Based upon an analysis of in vitro constituent cytotoxicity, in vivo post black salve histology, and experience with Mohs paste, black salve is likely to possess normal tissue toxicity with some cancer cell lines being relatively resistant to its effects. This may explain the incongruous case study reports of excessive scarring, deformity, and treatment failure.

Carcinogenic potential of sanguinarine, a phytochemical used in 'therapeutic' black salve and mouthwash.

Black salves are escharotic skin cancer therapies in clinical use since the mid 19th century. Sanguinaria canadensis, a major ingredient of black salve formulations, contains a number of bioactive phytochemicals including the alkaloid sanguinarine. Despite its prolonged history of clinical use, conflicting experimental results have prevented the carcinogenic potential of sanguinarine from being definitively determined. Sanguinarine has a molecular structure similar to known polyaromatic hydrocarbon carcinogens and is a DNA intercalator. Sanguinarine also generates oxidative and endoplasmic reticulum stress resulting in the unfolded protein response and the formation of 8-hydroxyguanine genetic lesions. Sanguinarine has been the subject of contradictory in vitro and in vivo genotoxicity and murine carcinogenesis test results that have delayed its carcinogenic classification. Despite this, epidemiological studies have linked mouthwash that contains sanguinarine with the development of oral leukoplakia. Sanguinarine is also proposed as an aetiological agent in gallbladder carcinoma. This literature review investigates the carcinogenic potential of sanguinarine. Reasons for contradictory genotoxicity and carcinogenesis results are explored, knowledge gaps identified and a strategy for determining the carcinogenic potential of sanguinarine especialy relating to black salve are discussed. As patients continue to apply black salve, especially to skin regions suffering from field cancerization and skin malignancies, an understanding of the genotoxic and carcinogenic potential of sanguinarine is of urgent clinical relevance.

Infiltrating basal cell carcinoma: a stellate peri-tumor dermatoscopy pattern as a clue to diagnosis.

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.

Keratoacanthoma versus invasive squamous cell carcinoma: a comparison of dermatoscopic vascular features in 510 cases.

INTRODUCTION: Keratoacanthoma (KA) and invasive squamous cell carcinoma (SCC) are keratinocytic tumors displaying vascular features, imaged using dermatoscopy. OBJECTIVE: Compare the dermatoscopy vascular features of KA to SCC. METHODS: This prospective study examined consecutive cases of 100 KA and 410 invasive SCC in a single private practice in Sydney, Australia. Vascular features were recorded in vivo direct from patients using a non-polarized Delta 20 Heine dermatoscope. These vascular features were: linear, branching, serpentine, hairpin, glomerular and dot vessels, the presence or absence of large diameter tumor vessels, vessel presence in central verses peripheral tumor areas and tumor pink areas in different proportions. Following full excision, all cases were submitted for histopathologic diagnosis. RESULTS: Branching vessels were the only vessel morphology that varied, with a significant incidence in KA (25.0%), compared to SCC (10.7%), P < 0.01. Large vessels were identified in 20.0% of KA, compared to 12.4% in SCC, P = 0.05. No vessels were observed in the central tumor areas in 43.4 % of KA compared to 58.0% of SCC, P = 0.01. Other data comparing the central versus peripheral tumor areas for vessels present did not reveal any distinctive associations. There were no significant differences between KA and SCC when reviewing the selected proportions of pink within the tumor. LIMITATIONS: The vascular features may be confounded by tumor depth in KA. Polarized dermatoscopy may not produce the same findings. CONCLUSION: This study found branching vessels to have a higher incidence in KA compared to invasive SCC. Although not statistically significant, large diameter vessels were also more frequent in KA. Proportions of pink within the tumor or central verses peripheral tumor vessel distribution were not useful diagnostic features separating KA from SCC using dermatoscopy.