Basosquamous Carcinoma: Comprehensive Clinical and Histopathological Aspects, Novel Imaging Tools, and Therapeutic Approaches.

Basosquamous carcinoma (BSC), an uncommon and aggressive nonmelanoma skin cancer exhibiting characteristics ranging from basal cell carcinoma (BCC) to squamous cell carcinoma (SCC), is a subject of controversy in terms of its classification, pathogenesis, histologic morphology, biologic behavior, prognosis, and management. This narrative review is based on an electronic search of English-language articles in PubMed that included the terms "basosquamous carcinoma" and/or "metatypical carcinoma of the skin" in their titles. The review aims to succinctly present and assess current data on the epidemiology, clinical presentation, dermoscopic, LC-OCT, and histopathologic characteristics, as well as the genetics and management of BSC, providing insight into this intriguing entity. As a conclusion, dermoscopy, deep incisional biopsies, and immunohistologic techniques should be applied in clinically suspicious lesions to achieve an early diagnosis and better prognosis of this tumor. Surgical treatments, including wide excision and Mohs' micrographic surgery, remain the treatment of choice. Finally, Hedgehog pathway inhibitors and checkpoint inhibitors, must be thoroughly investigated with large controlled trials, since they may offer an alternative solution to irresectable or difficult-to-treat locally advanced cases of basosquamous carcinoma.

Case Report: Basaloid Squamous Cell Carcinoma of the Tongue: A Case Report.

Basaloid squamous cell carcinoma (BSCC) is a rare variant of conventional squamous cell carcinoma (SCC) frequently affecting the upper aerodigestive tract. The hypopharynx, tonsil, supraglottic larynx, tongue (base), and head-neck regions are particularly susceptible to BSCC. Clinically, the presentation of BSCC and conventional SCC is similar, but BSCC has a poorer prognosis. BSCC is distinguished histopathologically by a dimorphic pattern, a distinctive basal cell component paired with a squamous component. However, its similar features to conventional SCC makes it difficult to diagnose. Therefore, histopathology and immunohistochemistry play a crucial role in diagnosing such tumors. Here we present the case of a 70-year-old male diagnosed with BSCC involving the tongue.

How to spot a basosquamous carcinoma: a study on demographics, clinical-dermatoscopic features and histopathological correlations.

Basosquamous carcinoma (BSC) is a relatively rare type of neoplasm originating from basal cell carcinoma with features of squamous differentiation. BSC has an aggressive local behaviour with a tendency for recurrence and a less frequent metastatic potential The primary objective was to describe the dermatoscopic features of the tumour. Secondary goals were to detect the morphological features of the tumour along with patients' characteristics and to evaluate possible dermatoscopic and histopathological correlations Twenty-two patients with 25 BSCs were enrolled. All tumours were surgically excised and diagnosis was based on histopathology. Clinical and dermatoscopic images were evaluated by two investigators based on pre-defined criteria, and a statistical analysis was performed The median age of the patients was 78 years old (range: 52-88) and the male/female ratio was 2.14. All patients reported history of either occupational (50%) or recreational (50%) intensive sun exposure and 72.73% had signs of actinic keratosis. The most common anatomical site of the tumours was the head/neck area (72%). Clinically, nodular (64%), ulcerated (88%) and non-pigmented (76%) lesions prevailed. Dermatoscopically, 92% had prominent vasculature and monomorphous arborizing vessels with a diffuse arrangement, representing the most frequently observed type. Ulceration (88%), SCC dermatoscopic criteria (56%), white strands/blotches (56%) and features of pigmentation (40%) were also detected We suggest that the most common prototype of BSC is an ulcerated, facial nodule in elderly males with photo-damaged skin, dermatoscopically displaying combined features of mostly nodular BCC and, to a less extent, SCC.

Preferentially expressed antigen in melanoma expression in nonmelanoma skin cancers and melanocytes in surrounding skin.

BACKGROUND: Immunohistochemistry for preferentially expressed antigen in melanoma (PRAME) has been studied in melanocytic lesions but not nonmelanoma skin cancers (NMSCs). This study evaluated PRAME expression in NMSCs and dermoepidermal junction (DEJ) melanocytes in the surrounding skin. METHODS: Ninety-nine NMSCs were studied: 23 Merkel cell carcinomas (MCCs), 25 well to poorly differentiated squamous cell carcinomas (SCCs), 14 basal cell carcinomas (BCCs), five basosquamous carcinomas, four sebaceous carcinomas, ten atypical fibroxanthomas, 11 dermatofibrosarcoma protuberans, and seven leiomyosarcomas. Staining quality was considered low or high intensity. Staining quantity was reported as negative 0%, 1% to 24%, 25% to 50%, and >50%. DEJ melanocyte PRAME expression was recorded. RESULTS: Forty-eight percent of NMSCs showed PRAME expression, mostly low intensity in fewer than 25% of cells. High-intensity expression was noted in one poorly differentiated SCC, six BCCs, and seven MCCs. Only MCCs showed expression in greater than 25% of tumor cells. Focal DEJ melanocytes expressed high-intensity PRAME in 18% of cases, most commonly SCCs (11/23). CONCLUSIONS: PRAME is negative or expressed with low intensity in a small percentage of NMSCs, with the exception of some MCC showing high-intensity and diffuse staining. Focal DEJ melanocytes showed high-intensity PRAME reactivity in the skin surrounding some NMSCs.

Skin tumors in xeroderma pigmentosum: Evaluation of a large series and a literature review.

BACKGROUND: Xeroderma pigmentosum (XP) is a rare genodermatosis with a lifelong propensity to develop malignant skin tumors. METHODS: In this retrospective study, 24 XP patients were evaluated with regard to frequency and clinicopathological features of benign and malignant skin tumors. RESULTS: Seventeen patients had at least one malignant skin tumor diagnosed: basal cell carcinoma (BCC) in 13 patients (n = 72), basosquamous carcinoma in three patients (n = 4), squamous cell carcinoma in six patients (n = 13), keratoacanthoma in three patients (n = 15), and melanoma in six patients (n = 18). Most melanomas (n = 15) were in situ lesions. Several benign skin tumors were noted such as tricholemmoma (n = 1), trichoepithelioma (n = 1), trichoblastoma (n = 1), follicular infundibulum tumor (n = 1), keratoacanthoma-like follicular lesion (n = 1), adnexal tumors with folliculosebaceous (n = 1) and tricholemmal differentiation (n = 1), and neurofibroma (n = 1). Benign vascular proliferations including pyogenic granulomas (n = 8), widespread telangiectasias, and senile angioma-like lesions were also observed in 3, 5, and 5 patients, respectively. CONCLUSIONS: Similar to many reports, BCC was found to be the most common malignant skin tumor. The high prevalence of benign adnexal tumors of follicular differentiation, some of them showing mixed histopathological features and various vascular proliferations in our series raises the question of whether they indicate a formerly undescribed association with XP.

Clinical and epidemiological analysis of basosquamous carcinoma: results of the multicenter study.

Basosquamous carcinoma (BSC) is a rare non-melanoma skin cancer that shares the characteristic features of both basal and squamous cell carcinomas (BCC, SCC). Our research enables better characterization of BSC in comparison to high-risk subtypes of BCC and SCC. Paper includes a retrospective analysis of BSC cases regarding sex, age, number of tumors and anatomical distribution in comparison to BCC and SCC evaluating the differences and defining the implications. Histologically confirmed carcinomas recorded between 1999 and 2019 were studied. 181 diagnosed BSC cases were identified, making this study the largest cohorts of BSC patients reported worldwide. Most cases were reported on head and neck. Analysis of facial anatomic distribution shows that most commonly affected sites were the nose (43%) and the cheek (25%). The age at excision of metatypical BCC was higher than those of low-risk BCC (P < 0.05), however similar to high-risk BCC (P = 0.20). We revisited that the concept of BSC is the most similar to high-risk subtypes of BCC. Patients with diagnosed BSC have higher risk of second nonmelanoma skin cancer. Therefore, the frequency of follow-up examination should be adjusted to the individual risk of another skin cancer.

Reappraising basosquamous carcinoma: a summary of histologic features, diagnosis, and treatment.

Basosquamous carcinoma (BSC) is a malignant and aggressive neoplasm with unclear molecular etiology. It is often misdiagnosed as basal cell carcinoma (BCC) or squamous cell carcinoma (SCC) on biopsy as there are unclear histologic criteria for this neoplasm. It has been interchangeably referred to as metatypical BCC and collision tumor, although these entities are different. On histology, BSC consists of basal cells with areas with nests of squamous cells and an intermediate transition zone. The nature of this transition zone is not clearly defined in literature; however, Ber-EP4 staining is diagnostic for BSC. A gradation of Ber-EP4 staining from strongly positive in basaloid areas to weakly positive in an intermediate zone is demonstrated (no staining of squamous areas). Treatment with an array of modalities including wide local excision, Mohs surgery, radiotherapy, and palliative chemotherapy has been performed. We recommend further molecular studies in understanding the genetic mechanisms leading to BSC. For the purpose of good clinical practice, multiple biopsies and immunohistochemical studies should be performed to avoid sampling error that can lead to a misdiagnosis of BSC.

Basosquamous carcinoma and melanoma collision tumor in a child with xeroderma pigmentosum.

Xeroderma pigmentosum (XP) is a rare autosomal recessive genodermatosis associated with hypersensitivity to ultraviolet radiation (UVR), being due to defects involving the nucleotide excision repair pathway. Patients with XP are prone to develop multiple cutaneous neoplasms including non-melanoma skin cancers and melanoma. Collision tumors in patients with XP have been reported in the literature including the following lesions, actinic keratosis, basal cell carcinoma, squamous cell carcinoma, and in situ melanoma. Herein, we present a rare collision tumor composed of melanoma and basosquamous carcinoma in a 13-year-old XP patient and describe the dermoscopic features.

Genetic Mutations Underlying Phenotypic Plasticity in Basosquamous Carcinoma.

Basosquamous carcinoma (BSC) is an aggressive skin neoplasm with the features of both basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). While genetic drivers of BCC and SCC development have been extensively characterized, BSC has not been well studied, and it remains unclear whether these tumors originally derive from BCC or SCC. In addition, it is unknown which molecular pathways mediate the reprogramming of tumor keratinocytes toward basaloid or squamatized phenotypes. We sought to characterize the genomic alterations underlying sporadic BSC to elucidate the derivation of these mixed tumors. We identifed frequent Hedgehog (Hh) pathway mutations in BSCs, implicating Hh deregulation as the primary driving event in BSC. Principal component analysis of BCC and SCC driver genes further demonstrate the genetic similarity between BCC and BSC. In addition, 45% of the BSCs harbor recurrent mutations in the SWI/SNF complex gene, ARID1A, and evolutionary analysis revealed that ARID1A mutations occur after PTCH1 but before SCC driver mutations, indicating that ARID1A mutations may bestow plasticity enabling squamatization. Finally, we demonstrate mitogen-activated protein kinase pathway activation and the loss of Hh signaling associated with the squamatization of BSCs. Overall, these results support the genetic derivation of BSCs from BCCs and highlight potential factors involved in modulating tumor reprogramming between basaloid and squamatized phenotypes.

A comparative analysis of clinicopathological factors between esophageal small cell and basaloid squamous cell carcinoma.

Esophageal small cell carcinoma (E-SmCC) and basaloid squamous cell carcinomas (BSCCs) are both highly aggressive malignancies, but their detailed differences in clinical behaviors have remained virtually unknown. In addition, treatment strategies of the patients with E-SmCC have not been established. 29 cases of E-SmCC and 39 with BSCC were examined in this study to clarify the clinical features and outcome of the patients with E-SmCC and to compare the findings with those of BSCC. E-SmCCs presented a more advanced status than BSCC (TNM Stage: P = .002). Esophagectomy was performed in 15 small cell carcinoma patients and 14 were treated with non-surgical/systemic therapy. The clinical outcome of the small cell carcinoma cases was significantly worse than those with BSCC (P = .001), but results of a stage-stratified analysis revealed that the Stage I small cell carcinoma patients presented favorable prognosis (3-year survival rate 100%, n = 4). In contrast, among those with Stage II-IV, clinical outcome tended to be better in the systemic therapy group (3-year survival rate 49%, n = 13) than the surgically treated group (3-year survival rate 0%, n = 12). E-SmCC was a more aggressive neoplasm than BSCC. However, early detection could possibly improve the clinical outcome of patients with E-SmCC. Systemic therapy could also benefit the patients with advanced disease (Stage II-IV).

Basal cell carcinoma and basosquamous carcinoma, two faces of the same condition?

Basal cell carcinoma (BCC) is the most common locally invasive malignant epidermal neoplasm. It is generally a tumor that runs a slow progressive course and can usually be cured by surgery. Basosquamous carcinoma is considered by some authors a rare subtype of BCC, while others describe it as independent tumor with different evolution from BCC. The aim of the study was to present a very interesting case of initially otherwise ordinary BCC that during its repeated and extensive relapses changed its histopathology in a basosquamous carcinoma, despite the free surgical margins and leading to major surgeries with loss of right eye. We present a case of 75-year-old male diagnosed in 2008 with a tumor located in the right naso-orbital region. The patient underwent surgical treatment, the histopathology being consistent with BCC. He presented recurrences of the tumor in 2009 and 2010 that were excised at approximately 9 and 16 months, respectively, from the first intervention. In 2010, the surgical procedure was radical, with removal of the tumor and the entire right superior eyelid. This approach proved to have negative side effects over the right eye in time. Therefore, after two months, a complete exenteration of the right orbit was necessary. The tumor recurred again for three times, after 20, 30 and 42 months from the first intervention and every time surgical treatment was applied. The microscopic inspection of the biopsies showed similarities between recurrences and initial tumor. In 2013, after 57 months from the first intervention, the patient was readmitted with a lesion in the same region that was excised but that time the histopathology differed from the previous, the tumor being composed of sheets of achromic epithelioid cells, with vesicular nuclei and prominent, eosinophilic nucleoli. The tumor cells were positive for pan-cytokeratin AE1∕AE3 and negative for S100 protein, human melanoma black 45 (HMB45) and vimentin that sustained the diagnosis of basosquamous carcinoma. The paper presented an interesting case with different histopathological features from a recurrence to other, with important implication in diagnosis and prognosis. The transformation of BCC into basosquamous carcinoma sustain that the basosquamous carcinoma is better a rare, aggressive variant of BCC, than an individual lesion.

Discordant molecular subtype classification in the basal-squamous subtype of bladder tumors and matched lymph-node metastases.

Molecular subtypes of muscle-invasive bladder tumors have emerged as a promising research tool with potential to stratify patients for neoadjuvant treatment. Prior to radical cystectomy, the utility of molecular classification and biomarkers depend on concordance between tissue from transurethrally resected specimens and disseminated disease. We assess the concordance of molecular subtypes and a large number of potential biomarkers in 67 pairs of muscle-invasive bladder tumors and synchronous lymph-node metastases. Tissue cores were stained for 29 immunohistochemistry markers and immunohistochemistry-based molecular subtype classification was performed. Molecular subtype was determined by mRNA profiling for 57 bladder tumors and 28 matched lymph-node metastases. Full section immunohistochemistry was performed to assess intra-tumor subtype heterogeneity in discordant cases, and exome sequencing was performed for 20 sample pairs. Discordant subtype classification between the bladder tumor and lymph-node metastasis was generally rare (12/67, 18%), but most (7/12, 58%) involved the Basal/Squamous-like subtype. Discordant Basal/Squamous-like tumors showed either Urothelial-like or Genomically Unstable, luminal-like phenotype in the lymph-node metastasis. Full section immunohistochemistry revealed intra-tumor subtype heterogeneity for six discordant cases including four involving the Basal/Squamous-like subtype. Subtype concordance for non- Basal/Squamous-like tumors was 91%. RNA-based classification agreed with immunohistochemistry classification but quantitative assessment is necessary to avoid false detection of subtype shifts. Most high confidence cancer mutations were shared between samples (n = 93, 78%), and bladder tumor private mutations (n = 20, 17%) were more frequent than those private to the lymph-node metastasis (n = 7, 6%). We conclude that bladder tumors and lymph-node metastases have overall similar molecular subtype, biomarker expression, and cancer mutations. The main exception was tumors of the Basal/Squamous-like subtype where most cases showed discordant classification, some with evidence of intra-tumor heterogeneity. The data are of relevance for neoadjuvant treatment stratification and raises questions on the dynamics of molecular subtypes during bladder cancer progression.

Sentinel lymph node metastasis in primary cutaneous basosquamous carcinoma. A cross-sectional study.

BACKGROUND AND OBJECTIVES: Basosquamous carcinoma (BSC) is a rare, biologically aggressive tumor. This cross-sectional study aims to define risk factors for subclinical nodal metastasis in primary BSC, and identify the patients who would benefit from routine sentinel node biopsy (SLNB) as part of the initial management. METHODS: A total of 142 patients, with histologically proven BSC without palpable lymph nodes, underwent SLNB after the initial excision. Clinicopathological features and demographics were analyzed between the patients with detected micrometastasis (SLNM) and those with negative SLN. RESULTS: In 7.7% patients, subcapsular and <0.1 mm SLNM were found. The frequency of SLNM was 0.9%, 11.8%, and 80.0% in patients with maximum lesion diameter ≤ 2 cm, 2.1-3.0 cm and >3.0 cm, respectively (P < 0.001) and was strongly associated with perineural (P < 0.001; OR = 26.46, 95% CI = 5.62-124.52) and lymphatic invasion (P < 0.001; OR = 17.35, 95% CI = 4.44-67.91). Within 18-84 months, no recurrence or metastasis were observed in SLNM positive patients. False negative SLNB rate of 15.4% was recorded. CONCLUSION: Cutaneous BSC is associated with early nodal metastatic potential. Tumor size >2 cm, lymphatic and perineural invasion are significant determinants for SLN micrometastasis. In the absence of palpable lymphadenopathy, wide resection and SLNB with long-term follow-up are highly recommended in these patients.

Primary basosquamous carcinoma of the lower eyelid with ocular invasion A case report.

INTRODUCTION: Ocular invasion is extremely rare for a primary eyelid Basosquamous Carcinoma (BSC). It can however occur in neglected cases if the clinical signs are overseen and the BSC is misdiagnosed for a less aggressive skin carcinoma. MATERIALS AND METHODS: A 58-year-old man suffering from an inferior eyelid BSC that had been neglected for 7 years was referred to our clinic. A local infiltration of the maxillary sinus and the contents of the orbit by the tumor was discovered, and he was managed with a left orbital exenteration and resection of the involved orbital bone. A follow up was established. DISCUSSION: BSC is a rare type of skin malignancy which as an entity rests between Basal Cell Carcinoma (BCC) and Squamous Cell Carcinoma (SCC), and its aggressive nature is often greater than that of the BCC and the SCC. Having no specific clinical features differentiating it from other BCC types, it can only be diagnosed by an adequate biopsy. Its early diagnosis is crucial in diminishing it's recurrence rate and it's metastatic potential. The standard therapeutical approach is the complete excision of the tumor, best performed by Mohs micrographic surgery. In cases of ocular infiltration, orbital exenteration is also usually necessary. CONCLUSIONS: Suspect, rapidly growing skin lesions should alert clinicians and an adequate biopsy should be performed. Regarding BSC, prompt and complete excision along with systemic exclusion of metastases and a close follow up are necessary. Adjuvant radiotherapy and chemotherapy could be beneficial to the patients. KEY WORDS: Basosquamous carcinoma (BSC), Basal cell carcinoma (BCC), Eyelid tumor, Ocular tissue invasion, Imiquimod, Maxillectomy, Metatypical basal cell carcinoma, Mohs micrographic surgery, Orbital exenteration, Orbit invasion, Squamous cell carcinoma (SCC), Vismodegib.

Periungual basal cell carcinoma.

Periungual basal cell carcinoma is rare and needs to be differentiated from other common diseases that affect this region. Several factors are associated with the development of this tumor, and sun damage seems to play an important role in its pathogenesis. Dermoscopy of clinically indolent lesions on the nail unit can shorten the diagnostic process and avoid destructive treatment and functional damage.