Successful Treatment of Giant Basal Cell Carcinoma with Topical Imiquimod 5% Cream with Long Term Follow-up

The use of the topical Imiquimod 5% cream offers a noninvasive, nonsurgical, and an effective option for the treatment of primary small (<2 cm) superficial basal cell carcinoma (sBCC). However, reports about successful treatment of giant (>5 cm) BCC with topical Imiquimod 5% cream are rare. We present our experience in the treatment of two giant tumors (6 × 8 cm², 5.2 × 4.2 cm²) of BCC on the face with Imiquimod 5% cream, 2 to 3 days/week for 12 weeks. Both the tumors were cured with clinical and pathological evidence, one with 6-year follow-up and the other with 3.5-year follow-up.     

Characteristics of Mixed Type Basal Cell Carcinoma in Comparison to Other BCC Subtypes

Background:

There are limited data exploring the characteristics of mixed type basal cell carcinoma (BCC).

Objectives:

To explore different characteristics of mixed type BCC.

Design:

Cross sectional study.

Materials and Methods:

825 patients with BCC enrolled in this study.

Results:

Among 825 patients, 512 (62%) were male. Three hundred and fifty five (43%) presented with nodular subtype, 267 (32.4%) with mixed subtype, 25 with superficial and the 178 remaining presented with other subtypes. Four hundred and eighty three (58.6%) of the lesions were on the face, 243 (29.5%) on scalp, 52 (6.3%) on ears, 20 (2.4%) on neck, 15 (1.8%) on trunk and 12 (1.4%) on extremities. Anatomic distribution of mixed type was as follows: 137 on face, (51.4%), 100 (37.3%) on scalp, 19 (7%) on ear, 6 (2.1%) on neck, 4 (1.5%) extremity and 1 (0.7%) on trunk, which the difference from non mixed types was statistically significant (P = 0.002). The mean diameter of the mixed types and non mixed type BCCs were significantly different (2.7 ± 2.1 cm vs. 2.2 ± 1.6 cm; P = 0.01. The prevalence of necrosis in mixed type BCC was two times higher than non mixed type BCCs (OR = 2.3, CI 95% 1.3-3.9, P = 0.001). The most frequent combined subtypes were nodular-infiltrative (P < 0.001).

Conclusion:

Mixed type BCC has differences with other BCC subtypes in anatomical distribution and tumor diameter. Indeed, mixed type BCCs are frequently composed of aggressive subtypes than nonaggressive subtypes.     

Periungual Basal cell carcinoma: a case report with review of literature

Basal cell carcinomas (BCCs) are considered to be uncommon around the nail plate. An indolent lesion of this region should arouse suspicion of potential malignancy and a skin biopsy should be undertaken without delay. Early diagnosis can enable the physician to render simpler nondestructive modalities of treatment. In this article, we describe such a case of longstanding BCC of this region mimicking a traumatic ulcer. The nature of the ailment was finally discovered on biopsy and the carcinoma was initially treated with topical Imiquimod.     

The Rate and Pattern of Bcl-2 and Cytokeratin 15 Expression in Trichoepithelioma and Nodular Basal Cell Carcinoma: A Comparative Study

Context:

Histopathological evaluations can differentiate between clinically resembling trichoepithelioma (TE) and basal cell carcinoma (BCC) unless the biopsy specimens are small or superficial. Previous studies used immunohistochemical evaluation for Bcl-2 and cytokeratin 15 (CK15), in attempts to differentiate between these two entities, with heterogeneous findings.

Aims:

This study intended to compare the rate and patterns of Bcl-2 and CK15 expressions between specimens of TE and nodular BCC.

Settings and Design:

Case-series including formalin-fixed, paraffin-embedded cutaneous biopsies.

Subjects and Methods:

Twenty-two BCC and 12 TE specimens were stained for Bcl-2 and CK15 and examined microscopically. The rate and patterns of expressions were compared between the two groups.

Statistical Analysis Used:

Statistical analysis was performed using the statistical software (SPSS version 16.0; SPSS Inc., Chicago, IL, USA), Pearson Chi-square, or Fisher''s exact tests, wherever appropriate.

Results:

The two groups were comparable for the expression rate and patterns of Bcl-2 (86.4%: 5 central, 14 diffuse in BCC vs. 83.3%: 2 central, 8 diffuse in TE; P = 0.59 and 0.54 for rate and pattern, respectively). The rate of CK15 expression was significantly higher in TE specimens (66.7%: 4 central, 3 diffuse, 1 peripheral vs. 4.5%: 1 central; P < 0.001). The positive likelihood ratio in distinguishing the two neoplasms was 14.7 (95% confidence interval: 2.1-103.7).

Conclusions:

CK15 but not Bcl-2 staining may help in differentiating between BCC and TE even in BCCs with follicular differentiation.     

Imiquimod 5% cream for the treatment of superficial and nodular basal cell carcinoma: randomized studies comparing low-frequency dosing with and without occlusion

BACKGROUND: Imiquimod 5% cream has been investigated for non-surgical treatment of superficial and nodular basal cell carcinoma (BCC) tumours. OBJECTIVES: Two studies were conducted to examine the effect of occlusion at low dosing frequencies on the safety and efficacy of topical imiquimod 5% cream for the treatment of superficial and nodular BCC. PATIENTS AND METHODS: Both open-label studies were conducted in Europe. Patients diagnosed with BCC were enrolled into either the superficial (93 patients) or nodular (90 patients) study, depending on the histological confirmation of the patient's tumour subtype. Patients were randomized to one of four groups to apply imiquimod 5% cream 2 or 3 days per week either with or without occlusion. Six weeks following a 6-week treatment period, the entire target tumour area was excised and histologically examined for evidence of residual tumour. RESULTS: In both studies, the highest histologically complete response rate was seen in the 3 days per week with occlusion groups, with complete response rates of 87% and 65% for the superficial and nodular studies, respectively. Occlusion did not have a statistically significant effect on response rate at either dosing frequency. Response rates for superficial and nodular BCC tumours treated 3 days per week without occlusion were 76% and 50%, respectively. CONCLUSIONS: In the superficial study, the complete response rate of 87% in the 3 days per week with occlusion group was similar to that of daily and 5 days per week dosing without occlusion in a previous 12-week study and one study of daily dosing without occlusion for 6 weeks. All treatment groups had acceptable safety profiles in both studies. Occlusion did not have a statistically significant effect on efficacy for either superficial or nodular BCC tumours.     

Nodulocystic Basal Cell Carcinoma Arising Directly from a Seborrheic Keratosis: A Rare Case Report

Seborrheic keratoses (SKs) are common epidermal tumors composed of benign keratinocytes. Malignant skin tumors including basal cell carcinoma (BCC) rarely arise within SKs. We report a rare case of an 82-year-old man with nodulocystic BCC that appeared at the center of a scaly hyperpigmented SK that had been presented for more than 10 years. It was histologically confirmed that CK19-positive BCC arose directly from the wall of the pseudohorn cyst, a part of the SK. Nodular and/or cystic BCC also rarely arise within SKs while the most common histologic type of BCC within SKs is the superficial type. Careful observation of SKs is important even though it is rarely a background condition for malignant transformation.     

Imiquimod 5% cream as pretreatment of Mohs micrographic surgery for nodular basal cell carcinoma in the face: a prospective randomized controlled study

Background Imiquimod 5% cream can reduce or clear superficial and small nodular basal cell carcinoma (BCC). It could be used as a pretreatment of Mohs micrographic surgery (MMS) to decrease defect size. Objectives To study if a pretreatment with imiquimod 5% cream decreases defect size after MMS. In addition, to study the effect on the number of Mohs stages and reconstruction time. Methods Seventy patients aged >18 years with a primary nodular BCC in the face were included. The imiquimod group used imiquimod 5% cream for 4 weeks, before MMS. The control group was treated with MMS only. Tumour and defect sizes were measured. We noted the number of Mohs stages, reconstruction time and side‐effects. Results The median percentage increase in area from tumour size at baseline to the post‐MMS defect for the imiquimod group was significantly less compared with the control group, 50% vs. 147% (P < 0·001). A tendency towards fewer Mohs stages in the imiquimod group was observed and the reconstruction time was significantly shorter in this group (P = 0·01). Conclusions Imiquimod 5% cream as pretreatment of MMS significantly reduced the tumour size in primary nodular BCC and reduced the surgical defect size. Further research is necessary to investigate cost‐effectiveness.     

Open study of the efficacy and mechanism of action of topical imiquimod in basal cell carcinoma

Imiquimod is an immune-response modifier that has been shown to be effective in the treatment of superficial and nodular basal cell carcinoma (BCC). The objective of this open-label study was to investigate the effectiveness of imiquimod 5% cream in superficial, nodular, and infiltrative BCC. Fifty-five Caucasian patients with primary BCC measuring 8 mm or more in diameter with a superficial, nodular, or infiltrative histological pattern were included in the study. Four groups of BCC (A, B, C, and D) and two dosing regimens were studied: 35 BCCs (groups A, B, and C) were treated with imiquimod three times weekly and 20 BCCs (group D) were treated with imiquimod five times weekly. Histological samples were obtained before treatment, during treatment (on day 22 in group A, day 15 in group B, and day 8 in groups C and D), and 6 weeks after treatment. All patients were followed-up for a minimum of 2 years. In the biopsy specimens obtained, the expression of Bcl-2, p53, and Ki-67, apoptotic index (Tunel technique), and the number of CD3+, CD8+, CD20+, CD56+, CD68+, granzyme B+, and S-100+ cells in the peritumoural inflammatory infiltrate, were determined and quantified. Of the 55 BCCs treated with imiquimod 41 (74%) were in complete remission after 2 years of follow-up. These comprised 4/4 superficial BCCs, 7/8 (88%) nodular BCCs, and 30/43 (70%) infiltrative BCCs. Multi-variate analysis demonstrated that baseline tumour size was the most powerful independent prognostic variable (P < 0.05). Treatment with imiquimod increased the apoptotic index (P < 0.05), reduced Bcl-2 expression (P < 0.05), and increased the number of CD3+, CD8+, CD20+, CD68+, granzyme B+, and S-100+ cells in the inflammatory infiltrate of the BCC (P < 0.05). In conclusion, imiquimod induced an antitumour immune response mediated by lymphocytes and macrophages, reduced Bcl-2 expression and increased the apoptotic index of BCC, and was clinically effective in 74% of BCCs after a 2-year follow-up period.     

Imiquimod 5% cream (Aldara) in the treatment of basal cell carcinoma

Skin cancer, the most common human cancer, is now a global epidemic. The most prevalent form of nonmelanoma skin cancer is basal cell carcinoma (BCC), the incidence of which continues to increase prompting development of new treatment modalities designed to add or complement current therapies. Although destructive modalities continue to be an important treatment options for BCC, nondestructive measures are a welcome addition to our therapeutic choices. Imiquimod, a topical immune response modifier, belongs to the family of immunostimulators. It enhances both the innate and acquired immune response, and has successfully treated both superficial and nodular basal cell carcinomas through the localized activation of elaborate immune response. Imiquimod can either be used alone or in combination with other treatment modalities. The most common adverse effects of topical use of imiquimod are localized to the site of application and easily managed.     

Basal cell carcinoma progression correlates with host immune response and stromal alterations: a histologic analysis

Neoplastic progression is characterized in part by escape from immune surveillance and formation of growth-permissive stroma. Basal cell carcinoma (BCC) can be subclassified into low- and high-risk types for local recurrence. To determine whether these types of BCC correlate with alterations in local host immune response and stroma and whether these changes follow stepwise histologic progression from low- to high-risk subtypes, we assessed the clinicopathologic features in 175 consecutive primary (nonrecurrent) BCC excision specimens. BCCs exhibited a significantly higher frequency of mixed rather than homogeneous growth patterns (76% vs. 24%, P=0.0001). Nodular (84%) was the most common pattern identified followed by superficial (77%), infiltrative (27%), morpheic (5%) and micronodular patterns (4%). Only superficial (12% of all BCC) and nodular (12%) patterns were identified in BCC with a homogeneous histologic phenotype. Micronodular and infiltrative-morpheic patterns were not identified together in mixed patterned BCCs, and these high-risk types were contiguous with nodular BCC. Superficial predominant BCC (major growth pattern) was significantly associated with trunk and extremity location (76%) and skin without solar elastosis (82%), whereas BCC harboring a nodular growth pattern component was significantly associated with a head and neck location (63%) and the presence of adjacent solar elastosis (all P< or =0.03). Significant correlations were identified for BCC subtypes with inflammatory and stromal alterations: superficial BCC with old regression and moderate to dense peritumoral lymphocytic infiltrates; high-risk types correlated with active regression; infiltrative and morpheic BCC with fibrosing tumor stroma; and micronodular BCC with loss of both host inflammatory and stromal tumor responses. Evaluating the theoretical histologic stepwise model of BCC progression (superficial-to-nodular-to-micronodular, or superficial-to-nodular-to-infiltrative-to-morpheic BCC types) revealed significant linear correlations with host response and alterations of tumor stroma (r=0.54, P=0.0001). BCC exhibit distinct epithelial-stromal-inflammatory patterns that correlate with BCC subtype and tumor progression. This ostensible pathway of diminishing host response and gain of permissive tissue environment highlights neoplastic evolution from low to high risk for local recurrence of BCC and implicates a histologic continuum reflecting dynamic host-BCC interactions.     

Comparison of risk factors of single Basal cell carcinoma with multiple Basal cell carcinomas

Background:

Basal cell carcinoma (BCC) is the most common malignant skin tumor. Although mortality attributable to BCC is not high, the disease is responsible for considerable morbidity. There is evidence that the number of patients who develop more than one BCC is increasing.

Aims:

The aim of this study was to elucidate possible risk factors for developing Multiple BCC.

Patients and Methods:

Patients with histologically proven BCC (n = 218) were divided into two groups (single BCC and Multiple BCC) according to the number of their tumors and their profile were reviewed. Probable risk factors were compared between these two groups.

Results:

Among 33 evaluated risk factors, mountainous area of birth, past history of BCC, history of radiotherapy (in childhood due to tinea capitis), abnormal underlying skin at the site of tumor, and pigmented pathologic type showed significant differences between the two groups.

Conclusions:

The high rate of additional occurrences of skin cancers among patients with previously diagnosed BCC emphasizes the need of continued follow-up of these individuals. Those with higher risk require closest screening.     

Genital vitiligo following use of imiquimod 5% cream

Imiquimod is a small molecule with adjuvant pro-inflammatory effects that can be topically delivered as a cream for treating external genital and perianal warts. In our report, two Chinese males at the ages of 25 and 22 years were treated with imiquimod 5% cream for recurrent condyloma accuminatum, three times per week for 18 and 12. weeks, respectively. Depigmentation were noted and gradually enlarged in the treated areas after the two patients discontinued imiquimod. Therefore, clinicians should be made aware of the possible pigmentary changes associated with application of this cream.     

Imiquimod: in superficial basal cell carcinoma

Imiquimod, available as a 5% cream, is a new topical treatment for adults with superficial basal cell carcinoma (BCC). The exact mechanism of action of imiquimod in superficial BCC is unknown. Imiquimod may act as a toll-like receptor-7 agonist, and is thought to exert its anti-tumor effect via modification of the immune response and stimulation of apoptosis in BCC cells. Topical imiquimod 5% cream effectively increased clinical and histologic clearance of single superficial BCC lesions compared with vehicle in patients enrolled in two large, well designed trials. Patients applied imiquimod five or seven times per week or vehicle for 6 weeks, and the composite clearance rates at 12 weeks post-treatment for the corresponding treatment groups were 75%, 73%, and 2%, respectively. In a trial investigating the long-term efficacy of imiquimod 5% cream following application five times per week for 6 weeks, a clinical clearance rate of 90% was reported at the initial 12-week post-treatment examination. The estimated rate of clinical clearance at the 1-year follow-up visit was 84%. Application site and local skin reactions were the most common adverse events reported by imiquimod recipients. The severity of erythema, erosion, and scabbing/crusting correlated positively with the composite and histologic response rates.     

Amelanotic Melanoma Masquerading as a Superficial Small Round Cell Tumor: A Diagnostic Challenge

Malignant melanoma poses a remarkable capacity for morphological diversity and often presents as a diagnostic challenge due to its wide clinical presentation. We present a case of a 73-year-old lady, with a large superficial ulcerative nodular mass on the flexor aspect of the right upper arm. On fine needle aspiration poorly differentiated round cell tumor was suggested, with histopathology also supporting the same diagnosis. A final diagnosis of amelanotic melanoma was given following immunohistochemical work-up using a panel of relevant markers. We are presenting this case, not only for its rare clinical presentation, but also for the diagnostic difficulties encountered by us in cytology and histopathology to reach the final diagnosis.     

5-氨基酮戊酸光动力治疗基底细胞癌疗效评价

目的:评价5-氨基酮戊酸光动力(ALA-PDT)治疗基底细胞癌的疗效及安全性.方法:回顾2016-2019年我院进行ALA-PDT治疗的17例基底细胞癌患者(浅表型14例,结节型3例)的临床资料.结果:14例浅表型基底细胞癌患者中13例患者皮损消退,仅留轻微色素沉着或色素减退,2例复发,1例于治疗后6个月后复发,1例于...     

Micronodular basal cell carcinoma: A distinct subtype? Relationship with nodular and infiltrative basal cell carcinomas

Micronodular basal cell carcinoma (BCC) may be more difficult to eradicate and prone to recurrence than nodular subtype. The aim of the study was to compare anatomical and histological characteristics of the basal cell carcinomas subtypes and the relationship of the micronodular BCC with other subtypes. Primary BCCs (n = 3074) were classified as superficial, nodular, micronodular, morpheic/infiltrative. The location was head/neck, limbs, chest/abdomen, back or genitals. Fifty‐one micronodular BCCs were matched randomly with nodular and infiltrative cases, by age, sex, and tumor site. A modified Clark level was used to classify the tumor depth. Micronodular, nodular and infiltrative BCC were prevalently located in the head/neck (P < 0.0001), while superficial in the other regions (P < 0.0001). The Clark level was comparable between micronodular and infiltrative BCC, while nodular BCC showed a more superficial level than micronodular (P < 0.001) and infiltrative (P < 0.001) BCC. No nodular BCC had level IV and only 37.3% level III, while 92% of both micronodular and infiltrative BCC were level III or IV. The percentage of level IV was 11.8% and 25.5% in micronodular and infiltrative BCC, respectively. In the mid‐face/periauricular region, 95.5% of micronodular and 100% of infiltrative cases of were level III or IV, compared to 50% of nodular BCC (P < 0.001). The Clark level of nodular subtype was higher for BCC of mid‐face/periauricular than other regions (P < 0.05). It can be concluded that micronodular BCC shows intermediate characteristics compared with nodular and infiltrative subtypes but appears to have a specific individuality making it a distinct subtype.     

Efficacy of photodynamic therapy with methyl aminolevulinate in the treatment of superficial and nodular basal cell carcinoma: an open-label trial

Photodynamic therapy with methyl aminolevulinate (MAL-PDT) is a non-invasive therapy for superficial and nodular basal cell carcinoma (BCC). We performed an open-label trial to evaluate efficacy, safety, tolerability and cosmetic outcome of MAL-PDT in selected patients with superficial and nodular BCCs. Ninety-four superficial and 24 nodular BCCs in 69 patients were treated with 2 to 8 MAL-PDT sessions. Efficacy, safety, tolerability and cosmetic outcome were evaluated at months 1, 3, 6 and 12 after the last MAL-PDT treatment and then every 3 months. One patient discontinued the study for reasons unrelated to study procedures. Complete clinical regression was detected in 84/94 (89.4%) superficial BCCs, and 12/23 (52.2%) nodular BCCs one month after 2 MAL-PDT sessions. No further clinical improvement was observed in either superficial or nodular BCCs with treatment continuation up to a maximum of 8 MAL-PDT sessions. Adverse effects were limited to mild local skin reactions, and cosmetic outcome was rated as excellent or good. Recurrence was observed in 2/84 (2.4%) successfully treated superficial BCCs at 6 and 12 months after treatment discontinuation. Based on the efficacy, tolerability, cosmetic outcome and recurrence rate, our results support the use of MAL-PDT for treatment of superficial BCC and for selected cases of nodular BCC.     

Imiquimod

? Imiquimod, available as a 5% cream, is a new topical treatment for adults with superficial basal cell carcinoma (BCC). The exact mechanism of action of imiquimod in superficial BCC is unknown. Imiquimod may act as a toll-like receptor-7 agonist, and is thought to exert its anti-tumor effect via modification of the immune response and stimulation of apoptosis in BCC cells. ? Topical imiquimod 5% cream effectively increased clinical and histologic clearance of single superficial BCC lesions compared with vehicle in patients enrolled in two large, well designed trials. Patients applied imiquimod five or seven times per week or vehicle for 6 weeks, and the composite clearance rates at 12 weeks post-treatment for the corresponding treatment groups were 75%, 73%, and 2%, respectively. ? In a trial investigating the long-term efficacy of imiquimod 5% cream following application five times per week for 6 weeks, a clinical clearance rate of 90% was reported at the initial 12-week post-treatment examination. The estimated rate of clinical clearance at the 1-year follow-up visit was 84%. ? Application site and local skin reactions were the most common adverse events reported by imiquimod recipients. The severity of erythema, erosion, and scabbing/crusting correlated positively with the composite and histologic response rates.