Non-Pigmented Adenoid Subtype of Basal Cell Carcinoma: A Case Report

ABSTRACTBackgroundHigh risk (HR) basal cell carcinoma (BCC) subtypes have been associated with high recurrence rates that is felt to be better managed surgically. Specifically, Mohs Micrographic Surgery (MMS) is considered most effective for aggressive HR BCCs and superior to traditional nonsurgical techniques, including radiation. Recently, superficial radiation therapy with high resolution ultrasound image guidance called Image Guided Superficial Radiation Therapy (IGSRT) displayed high local control (LC) rates and is an emerging non-surgical alternative to MMS for non-melanoma skin cancer (NMSC).ObjectivesWe present the largest experience in the USA on treatment of BCCs using IGSRT and specifically evaluate if there are differences in LC between HR BCC versus non-HR subtypes using this technology.MethodsA retrospective analysis was conducted on 7,994 BCC lesions treated with IGSRT in the continental United States. We compared the results of BCCs treated with IGSRT separated by HR vs non HR groups including 339 HR BCC lesions and 7655 non HR BCC lesions. High risk was defined as infiltrative, micronodular, morpheaform, and sclerosing subtypes. Non-HR BCC included superficial, nodular, and not otherwise specified (NOS) subtypes. Local control (LC) rates at two and five years were calculated with actuarial life-table and Kaplan-Meier methods and statistically compared using log rank tests.ResultsIGSRT treatment of the HR BCC group showed no recurrences with two and five-year actuarial and KM LC rates all at 100%. In comparison, the non-HR BCC cohort achieved similar two and five-year actuarial LC rates of 99.71% and 99.24% (KM LC at 99.5% and 99.23%), respectively. No statistical differences in LC rates between the two cohorts (p=0.278 each) resulted. Patients tolerated treatment well with little or rare high grade RTOG toxicity reported in both cohorts.ConclusionHR BCC may be treated just as effectively as low risk BCC using IGSRT and presents a viable alternative to MMS. The targeted approach using IGSRT, incorporating high resolution dermal ultrasound (HRDUS), appear to enhance treatment accuracy and effectiveness demonstrating high LC rates in all subtypes of BCC comparable to MMS and is a viable non-surgical option.Plain language summaryEffectiveness of a non-surgical skin cancer treatment using an image guided form of radiation modality on all subtypes of basal cell skin cancerRecent studies using a non-surgical treatment combining low penetrance radiation with ultrasound called Image Guided Superficial Radiation Therapy (IGSRT) showed promise in curing Basal Cell Cancer (BCC) of the skin, which is the most common skin cancer worldwide afflicting millions annually. Recent studies on early stage (I, II) BCCs treated with IGSRT (estimated combined total of ∼1900 BCC cases) appear to rival the best surgical treatment available called Mohs Micrographic Surgery (“Mohs” or MMS). Furthermore, certain subtypes of BCC appear to behave more aggressively with worse outcomes even with surgery and is generally felt inappropriate for radiation treatment. However, BCC subtypes were not specified in previous IGSRT studies.This study presents the largest experience (using medical chart review) in approximately 8000 BCC cases treated by IGSRT across the continental United States separated by aggressive vs non-aggressive subtypes for early stages (I, II) as well as more advanced (stage III) BCC cases to evaluate the efficacy and safety.This study confirms the high cure/control rate and safety of IGSRT for all subtypes of BCC which appear equivalent with Mohs (although the study was not meant to be a head to head comparison of the 2 different modalities). Moreover, the aggressive types of BCC showed similar (if not marginally better) cure rates than the more common non-aggressive BCC subtypes.The potential benefits to patients from this study show there is now a clinically proven non-surgical treatment with the same effectiveness as surgery for the most common cancer on the planet.Key PointsThis study provides evidence that backs up using IGSRT as a viable treatment option to MMS for both high risk and non-high risk BCC cases, achieving similar local control rates for both groups.It highlights that high risk BCC is more sensitive to radiation therapies such as IGSRT than previously believed, challenging the conventional practice of surgical treatment.

Red dot basal cell carcinoma is a distinctive clinical subtype of basal cell carcinoma. It has been reported in eight individuals with a male to female ratio of 1:1; and the patients’ ages ranged from 50 to 74 years. All patients had prior history of actinic keratoses and basal cell carcinoma. In addition, some patients also had prior squamous cell carcinoma, malignant melanoma, and/or dysplastic nevus. The tumor was usually of recent onset, asymptomatic, and on sun-exposed skin. It was most commonly located on the nose (five patients); other sites were the upper lip, the mid back, or thigh—each in one patient. The red dot basal cell carcinoma was solitary and small—usually 4 mm or less in diameter. It typically presented as a red macule or papule; however, it sometimes appeared as a flesh-colored or pink to light-red papule with a bright-red central area. Microscopic features showed basaloid tumor cells (arranged as either nodular aggregates or superficial buds or both). In the central portion of the lesion, there was a proliferation of erythrocyte-containing vascular spaces between the epidermis and the neoplasm. The basal cell carcinoma pathology subtype was either nodular and superficial (three patients), nodular (two patients), or superficial (one patient). The clinical differential diagnosis of red dot basal cell carcinoma included not only benign vascular lesions (such as hemangioma and telangiectasia) but also inflammatory conditions and adnexal tumors. Other basaloid cell neoplasms were in the pathologic differential diagnosis. The pathogenesis of red dot basal cell carcinoma is similar to that of other basal cell carcinoma clinical subtypes. Mohs surgery is the treatment of choice for red dot basal cell carcinomas. Red dot basal cell carcinoma has two categories of biologic behavior based on the ratio of the postoperative wound size as compared with the size of the preoperative tumor: nonaggressive (for which the ratio was 5:1 or less for three patients) and aggressive (for which the ratio was greater than 12:1 for three patients). There was no recurrence of the red dot basal cell carcinoma after treatment. In conclusion, the incidence of red dot basal cell carcinoma—a unique morphologic variant of basal cell carcinoma—may be higher than suggested by the number of reported patients with this basal cell carcinoma subtype.

Background: Basal cell carcinomas is one of the commonest cancer worldwide with a variable Nigerian prevalence of 7% to 20% of all histologically diagnosed cancers across Nigeria. Basal cell carcinoma has various histologic subtypes which can be divided into low risk and high risk subtypes. The low risk subtypes include Superficial basal cell carcinoma, Nodular basal cell carcinoma (adenoid, cystic and keratotic variant, Pigmented basal cell carcinoma, Fibroepithelial basal cell carcinoma and Infundibulocystic basal cell carcinoma (BCC with adnexal differentiation). They have low risk of recurrence, less proliferation and low potential for malignancy. While the high risk include; uperficial micronodular basal cell carcinoma, Infiltrating basal cell carcinoma, Sclerosing/morphoeaform basal cell carcinoma, Basosquamous basal cell carcinoma and Basal cell carcinoma with sarcomatoid differentiation. having higher ability to metastasize, proliferate rapidly and have invasive tendencies. Aims: This study analyzed the proliferative index using ki-67 immunoperoxidase protein of the histologic subtypes of basal cell carcinoma diagnosed in Federal Medical centre Umuahia, as to know the most dominant subtype of BCC and their proliferative index using Ki-67 in order to predict their biologic behaviors Methodology: Archival FFPE blocks were retrieved alongside relevant clinical data. Hematoxylin and Eosin as well as immunohistochemistry using monoclonal antibody against Ki-67 (BioCare RM325C(RM)) stains were done on fresh 4-micron sections of tumour specimens to determine the antigen expression. Result: The Ki-67 expression among the nodular variant of BCC, ranges from 1.2-15.2% with a mean value of 9.3%. The superficial variant expresses a Ki-67 expression value ranges from 2-18% with a mean value of 11.2%. The infiltrating variant of BCC has Ki-67 expression of a range of value from 14.4-28.2% with a mean value of 19.6%. Basosquamous variant has Ki-67 expression ranges from 21-45.6% with a mean value of 35.4%. The Sclerosing (morpheaform) variant has a Ki-67 expression ranging from 18- 32.7% with a mean value of 22.5%. The Proliferative index using Ki-67 nuclear stain of the low risk subtypes ranged from 1.2-18% with a mean value of 10%, while the high-risk subtypes have Proliferative index of 14.4-45.6% and a mean value of 25.1%.the most dominant variant is nodular BCC with the lowest proliferative index. Conclusion: The high grade subtypes of cutaneous BCC, (infiltrating, Morpheaform and basosquamous BCC) possess a significant high proliferative index as high as 45.6% for basosquamous variant, a proliferative index that can be found in high grade carcinomas and sarcomas. Therefore, there is need for critical evaluation and follow up for all cases of BCC in order to isolate those with high proliferative index and manage accordingly.

Background The role of dermoscopy in distinguishing the histopathological subtypes of basal cell carcinoma (BCC) is not fully elucidated. Aims To determine the accuracy of dermoscopy in diagnosing different BCC subtypes. Methods The dermoscopic features of 102 histopathologically verified BCCs were studied retrospectively. The tumours were classified as superficial (n=33,32.3%), nodular (n=46,45.1%) and aggressive (n=23,22.6%) BCCs by histopathology. Statistical analysis included Cohen's kappa test, proportion of correlation, measures of diagnostic accuracy, diagnostic odds ratio and the credibility ratio of positive (LR+) and negative (LR-) tests. Results The highest value in all performed tests was seen in superficial BCCs (kappa 0.85; proportion of correlation 93%; diagnostic accuracy 93.1%), good correlation was noted in nodular BCCs (kappa 0.62, proportion of correlation 80%; diagnostic accuracy 80.4%) but dermoscopic correlation with histopathology was low for aggressive BCCs (kappa 0.13; proportion of correlation 79%; diagnostic accuracy 78.4%). Short, fine telangiectasias (83.3%) showed the greatest importance for the diagnosis of superficial BCCs, blue-grey ovoid nests (61.8%) had the highest diagnostic accuracy in nodular BCCs, while arborising vessels (79.4%) was the most significant dermoscopic feature for the diagnosis of aggressive BCCs. Limitations This was a retrospective analysis and included only Caucasian patients from a single centre. Conclusion The highest agreement of dermoscopic features with the histologic type was found in superficial BCCs. We did not find any specific dermoscopic structure that could indicate a diagnosis of aggressive BCC. The presence of relevant dermoscopic features in the evaluated cases was determined by the depth of tumour invasion and not by its histology.

Imiquimod is a topical immune response modifier that has proved efficacious in the treatment of the superficial variant of basal cell carcinoma. The nodular variant of basal cell carcinoma has shown moderate response to imiquimod; other variants have not been tested. The mechanism of action is largely unknown; however, studies indicate the mechanism involves alteration of local cytokine production. The objective of this study is to evaluate the cytokine response of imiquimod in all variants of basal cell carcinoma. Ten patients were selected who had clinically and histologically proven basal cell carcinoma. All lesions were treated with imiquimod once a day, 5 days a week, for 3 weeks. After a 3-week rest period, the lesions were rebiopsied. All biopsy specimens were analyzed via polymerase chain reaction (PCR) for various cytokines. Nine of 10 lesions resolved clinically, which included nodular, superficial, infiltrative, adenoid, and micronodular variants. The cytokine with the greatest change pre- and post-treatment was IL-8, which decreased an average of 44 per cent (P = 0.06). We concluded that topical 5 per cent imiquimod is an effective treatment of various subtypes of basal cell carcinoma. IL-8, which plays an important role in the development and metastasis of melanoma, may be involved in the mechanism of action of imiquimod on cutaneous malignancies. Larger studies are needed to prove the efficacy of imiquimod on nonsuperficial variants of basal cell carcinoma and cutaneous melanoma metastasis.

Red dot basal cell carcinoma is a unique variant of basal cell carcinoma. Including the three patients described in this report, red dot basal cell carcinoma has only been described in seven individuals. This paper describes the features of two males and one female with red dot basal cell carcinoma and reviews the characteristics of other patients with this clinical subtype of basal cell carcinoma. A 70-year-old male developed a pearly-colored papule with a red dot in the center on his nasal tip. A 71-year-old male developed a red dot surrounded by a flesh-colored papule on his left nostril. Lastly, a 74-year-old female developed a red dot within an area of erythema on her left mid back. Biopsy of the lesions all showed nodular and/or superficial basal cell carcinoma. Correlation of the clinical presentation and pathology established the diagnosis of red dot basal cell carcinoma. The tumors were treated by excision using the Mohs surgical technique. Pubmed was searched with the keyword: basal, cell, cancer, carcinoma, dot, red, and skin. The papers generated by the search and their references were reviewed. Red dot basal cell carcinoma has been described in three females and two males; the gender was not reported in two patients. The tumor was located on the nose (five patients), back (one patient) and thigh (one patient). Cancer presented as a solitary small red macule or papule; often, the carcinoma was surrounded by erythema or a flesh-colored papule. Although basal cell carcinomas usually do not blanch after a glass microscope slide is pressed against them, the red dot basal cell carcinoma blanched after diascopy in two of the patients, resulting in a delay of diagnosis in one of these individuals. Dermoscopy may be a useful non-invasive modality for evaluating skin lesions when the diagnosis of red dot basal cell carcinoma is considered. Mohs surgery is the treatment of choice; in some of the patients, the ratio of the area of the postoperative wound to that of the preoperative cancer was greater than 12:1, demonstrating a significant lateral spread of the tumor beyond the observed clinical margins of the neoplasm. In conclusion, in a patient with a personal history of actinic keratosis or nonmelanoma skin cancer, the appearance of a new red dot in a sun-exposed site should prompt additional evaluation of the skin lesion to exclude or establish the diagnosis of red dot basal cell carcinoma.

Studies have reported the application of conventional optical coherence tomography (OCT) in the diagnosis of basal cell carcinoma (BCC). The new OCT provides cellular details similar to those in pathology slides and may reduce user learning time. This study aimed to demonstrate the quality of ex vivo full-field cellular-resolution OCT images and compare the diagnostic accuracy between physicians with varying pathology experience. Sixty histologically confirmed BCCs were selected. Tissue samples were sectioned and scanned using OCT, and their features were compared with those of hematoxylin and eosin (H&E)-stained sections. Thirty images were selected for the test administered to dermatology residents, dermatopathology fellows, and board-certified general pathologists without any OCT experience. The pretest learning included a 3-min instruction and 10-min self-study of four BCC variants. Histopathological BCC and normal histological features were clearly recognizable on the OCT images. The pathological BCC features observed in the OCT images correlated with those found in the H&E-stained sections. Seven participants completed the test. The correct answer rates of the residents, fellows, and pathologists were 71%, 68%, and 83% for BCC and 44%, 57%, and 57% for the BCC subtypes, respectively. All the participants identified BCC in >70% cases with a learning time of only 13minutes. The results indicated that cellular-resolution OCT provided high-quality images similar to the conventional pathology slides. Pathology experience did reflect the diagnostic accuracy. However, a longer training time is still needed at all levels to recognize the BCC subtypes correctly.

Basal cell carcinomas are the most common primary cutaneous malignant neoplasms. The diagnosis of basal cell carcinoma represents a common and routine task for pathologists and dermatopathologists. The aim of this review is the clinical and histopathological presentation of the most common subtypes of basal cell carcinoma. Furthermore, the rare variants of basal cell carcinoma and their differential diagnoses are also discussed.

Basosquamous Carcinoma of the Neck

Histopathological classification of basal cell carcinoma (BCC) has important prognostic and therapeutic implications, but reproducibility of BCC subtyping among dermatopathologists is poor. To obtain a consensus paper on BCC classification and subtype definitions. A panel of 12 recognized dermatopathologists (G12) from nine European countries used a modified Delphi method and evaluated 100 BCC cases uploaded to a website. The strategy involved five steps: (I) agreement on definitions for WHO 2018 BCC subtypes; (II) classification of 100 BCCs using the agreed definitions; (III) discussion on the weak points of the WHO classification and proposal of a new classification with clinical insights; (IV) re-evaluation of the 100 BCCs using the new classification; and (V) external independent evaluation by 10 experienced dermatopathologists (G10). A simplified classification unifying infiltrating, sclerosing, and micronodular BCCs into a single "infiltrative BCC" subtype improved reproducibility and was practical from a clinical standpoint. Fleiss' κ values increased for all subtypes, and the level of agreement improved from fair to moderate for the nodular and the unified infiltrative BCC groups, respectively. The agreement for basosquamous cell carcinoma remained fair, but κ values increased from 0.276 to 0.342. The results were similar for the G10 group. Delphi consensus was not achieved for the concept of trichoblastic carcinoma. In histopathological reports of BCC displaying multiple subtypes, only the most aggressive subtype should be mentioned, except superficial BCC involving margins. The three BCC subtypes with infiltrative growth pattern, characteristically associated with higher risk of deep involvement (infiltrating, sclerosing, and micronodular), should be unified in a single group. The concise and encompassing term "infiltrative BCCs" can be used for these tumors. A binary classification of BCC into low-risk and high-risk subtypes on histopathological grounds alone is questionable; correlation with clinical factors is necessary to determine BCC risk and therapeutic approach.

Desmoplastic trichoepithelioma (DTE), morpheaform basal cell carcinoma (BCC) and microcystic adnexal carcinoma (MAC) are sclerosing adnexal neoplasms with overlapping histopathologic features. We compared cytokeratin 15, (CK15), T-cell death-associated gene 51 (TDAG51), cytokeratin 20 (CK20) and androgen receptor (AR) in differentiating these tumors and assessed their expression in BCC subtypes. Fifteen DTE, 15 infundibulocystic BCC, 18 micronodular BCC, 18 morpheaform BCC and 6 MAC were assessed for CK15, TDAG51, CK20 and AR expression. Quantitative CK15 staining was higher in DTE compared with BCC (p < 0.0001) and MAC (p = 0.02). Quantitative TDAG51 staining was higher in DTE than BCC (p < 0.0001). The CK20+AR- immunophenotype was 100% sensitive and specific in diagnosing DTE. The CK20-AR+ immunophenotype was 95.24% specific and 83.33% sensitive for BCC. The CK20-AR- immunophenotype was 83.33% sensitive and 90.91% specific for MAC. CK15, CK20 and AR were positive in 87, 53 and 67% of infundibulocystic BCC cases, respectively. Combination of CK20 and AR best differentiated these sclerosing adnexal neoplasms. Greater positivity for CK15 and TDAG51 generally favors benign lesions. Infundibulocystic BCC has higher CK20 and lower AR immunopositivity than other BCC variants and a high degree of CK15 and TDAG51 positivity.

Simple SummaryBasal cell carcinoma is the most frequently occurring type of skin cancer. Its treatment can be either local or surgical depending on its subtype and extension, with early recognized and superficial cases being easier to treat. Some of them, however, display unspecific features, making diagnosis difficult. Non-invasive devices such as line-field confocal optical coherence tomography (LC-OCT) are able to recognize morphological features of different BCC subtypes with a good correlation to histopathology. We decided to study their application to clinically doubtful BCC cases.Diagnosing clinically unclear basal cell carcinomas (BCCs) can be challenging. Line-field confocal optical coherence tomography (LC-OCT) is able to display morphological features of BCC subtypes with good histological correlation. The aim of this study was to investigate the accuracy of LC-OCT in diagnosing clinically unsure cases of BCC compared to dermoscopy alone and in distinguishing between superficial BCCs and other BCC subtypes. Moreover, we addressed pitfalls in false positive cases. We prospectively enrolled 182 lesions of 154 patients, referred to our department to confirm or to rule out the diagnosis of BCC. Dermoscopy and LC-OCT images were evaluated by two experts independently. Image quality, LC-OCT patterns and criteria, diagnosis, BCC subtype, and diagnostic confidence were assessed. Sensitivity and specificity of additional LC-OCT were compared to dermoscopy alone for identifying BCC in clinically unclear lesions. In addition, key LC-OCT features to distinguish between BCCs and non-BCCs and to differentiate superficial BCCs from other BCC subtypes were determined by linear regressions. Diagnostic confidence was rated as “high” in only 48% of the lesions with dermoscopy alone compared to 70% with LC-OCT. LC-OCT showed a high sensitivity (98%) and specificity (80%) compared to histology, and these were even higher (100% sensitivity and 97% specificity) in the subgroup of lesions with high diagnostic confidence. Interobserver agreement was nearly perfect (95%). The combination of dermoscopy and LC-OCT reached a sensitivity of 100% and specificity of 81.2% in all cases and increased to sensitivity of 100% and specificity of 94.9% in cases with a high diagnostic confidence. The performance of LC-OCT was influenced by the image quality but not by the anatomical location of the lesion. The most specific morphological LC-OCT criteria in BCCs compared to non-BCCs were: less defined dermoepidermal junction (DEJ), hyporeflective tumor lobules, and dark rim. The most relevant features of the subgroup of superficial BCCs (sBCCs) were: string of pearls pattern and absence of epidermal thinning. Our diagnostic confidence, sensitivity, and specificity in detecting BCCs in the context of clinically equivocal lesions significantly improved using LC-OCT in comparison to dermoscopy only. Operator training for image acquisition is fundamental to achieve the best results. Not only the differential diagnosis of BCC, but also BCC subtyping can be performed at bedside with LC-OCT.

Background. The aim of this study was to investigate maspin and ezrin expression in different subtypes of periocular basal cell carcinoma (BCC). Methods. Tissue samples from 43 patients with periocular BCC. Our cases were comprised of 10 morpheaform, 25 nodular, and 8 adenoid type BCCs. Immunohistochemical staining for maspin and ezrin was performed by Envision detection system. Results. There was no difference between different subtypes of BCC in maspin expression regarding positivity, intensity, and pattern of expression. Ezrin was expressed in all subtypes of BCC but the intensity was significantly higher in morpheaform BCC compared to nodular and adenoid types (P < 0.001 and P = 0.012, resp.); ninety percent of morpheaform samples showed strong ezrin intensity, while this strong intensity was only present in 25% and 12% of adenoid and nodular subtypes, respectively. There was no correlation between age, sex, or tumor margin involvement and expression of neither maspin nor ezrin. There was no correlation between maspin and ezrin expression except in nodular type, in which an inverse correlation was found (P = 0.004). Conclusion. Ezrin is expressed intensely in morpheaform BCC of periocular region. Further studies are needed to show the significance of this finding in prognosis of morpheaform BCC.

Basal cell carcinoma (BCC) is the most common skin cancer, and its incidence is rising. Millions of benign biopsies are performed annually for BCC diagnosis, increasing morbidity, and healthcare costs. Non-invasive in vivo technologies such as multiphoton microscopy (MPM) can aid in diagnosing BCC, reducing the need for biopsies. Furthermore, the second harmonic generation (SHG) signal generated from MPM can classify and prognosticate cancers based on extracellular matrix changes, especially collagen type I. We explored the potential of MPM to differentiate collagen changes associated with different BCC subtypes compared to normal skin structures and benign lesions. Quantitative analysis such as frequency band energy analysis in Fourier domain, CurveAlign and CT-FIRE fibre analysis was performed on SHG images from 52 BCC and 12 benign lesions samples. Our results showed that collagen distribution is more aligned surrounding BCCs nests compared to the skin's normal structures (p < 0.001) and benign lesions (p < 0.001). Also, collagen was orientated more parallelly surrounding indolent BCC subtypes (superficial and nodular) versus those with more aggressive behaviour (infiltrative BCC) (p=0.021). In conclusion, SHG signal from type I collagen can aid not only in the diagnosis of BCC but could be useful for prognosticating these tumors. Our initial results are limited to a small number of samples, requiring large-scale studies to validate them. These findings represent the groundwork for future in vivo MPM for diagnosis and prognosis of BCC.

The diagnosis of basal cell carcinoma is histopathological, but there are dermatoscopic criteria that confer high sensitivity and specificity to help the clinician improve its identification. However, the basal cell carcinoma blue-white variant does not totally meet these dermatoscopic criteria, and thus can be confused with other pigmented tumors. In the literature reviewed, we found only five cases of this variant. The present objective is to describe the dermatoscopic characteristics of the blue-white variant of basal cell carcinoma observed in a tertiary dermatology institute. The dermatoscopy files of patients with a histopathological diagnosis of basal cell carcinoma between January 1, 2006 and December 31, 2015 were reviewed. A total of 32 cases with blue-white variant of basal cell carcinoma were observed over a period of 10 years. Of these cases, 97% presented dermatoscopic findings not included in the aforementioned criteria, such as whitish septa, structureless white areas, homogenous blue pigmentation and shiny white structures. The small sample size and the retrospective nature of the design. We consider it important for dermatologists to know this rare variant of basal cell carcinoma and to familiarize themselves with their dermatoscopic findings, in order to prevent erroneous diagnoses or inadequate treatments.