Treatment of locally advanced and metastatic basosquamous carcinoma, navigating among sonic hedgehog pathway inhibitors, immune checkpoint inhibitors, chemotherapy, and radiotherapy: A case series and literature review.

Locally advanced (laBSCs) and metastatic basosquamous carcinomas (mBSCs) represent a therapeutic challenge. By definition, these forms are not amenable to surgery or radiotherapy, but according to literature reports, sonic hedgehog pathway inhibitors (HHIs), anti-programmed death 1 receptor antibodies (anti-PD-1), and other treatment approaches involving chemotherapy, surgery, and radiotherapy have been used. This work features 5 real-life cases of advanced BSCs, treated at the Dermato-Oncology Unit of Trieste (Maggiore Hospital, University of Trieste). In addition, a review of the current treatment options reported in the literature for laBSC and mBSC is provided, collecting a total of 17 patients. According to these preliminary data, HHIs such as sonidegib and vismodegib could represent a safe and effective first line of treatment, while the anti-PD-1 cemiplimab may be useful as a second-line option. Chemotherapy and combined approaches involving surgery and radiotherapy have been also reported to be suitable in some patients.

Metastasis of a basosquamous carcinoma arising in a nevus sebaceus.

Nevus sebaceus (NS) is a congenital hamartoma of skin structures including the epidermis, sweat sebaceous glands, and hair follicles. It is known that secondary tumors can occur in NS. However, secondary metastatic malignancies are rare. Basosquamous carcinoma (BSC) is an aggressive type of basal cell carcinoma (BCC) characterized by squamous differentiation. Herein, we report a case of metastatic BSC that developed in a 73-year-old male with NS. The clinical presentation of this patient was that of an ulcerative nodule developing in a longstanding plaque-like lesion consistent with NS. Histopathological examination revealed characteristic features of BCC with some areas of squamous differentiation in addition to the structure of a typical NS. Immunohistochemical expression of Ber-EP4, AE1/AE3, and epithelial membrane antigen helped to make the diagnosis of BSC.

Line-field confocal optical coherence tomography of basosquamous carcinoma: a case series with histopathological correlation.

BACKGROUND: Basosquamous carcinoma (BSC) is a rare and potentially aggressive cutaneous neoplasm combining histopathological features of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Line-field confocal optical coherence tomography (LC-OCT) is a new, non-invasive imaging technique featuring excellent resolution and penetration. To date, studies about the use of LC-OCT in the BCC and SCC fields are available, but similar investigations are lacking in the BSC field. OBJECTIVE: The goal of the present study was to identify/describe LC-OCT criteria of BSC. METHODS: Consecutively enrolled BSCs were imaged with dermoscopy and LC-OCT prior to surgical excision. Dermoscopic and LC-OCT images were evaluated, and histopathological slides were reviewed. RESULTS: Six BSCs from six patients [four (66.7%) males and two (33.3%) females; mean age 76.5 (62-96) years] were included. Identified LC-OCT criteria for BSC included BCC-associated (dermal lobules with millefeuille pattern, dilated vessels, bright cells within the epidermis, bright cells within lobules, stromal stretching, stromal brightness) and SCC-associated features (acanthosis, hyperkeratosis, disarranged epidermal architecture, broad strands, elastosis and glomerular vessels). Interruption of the dermal-epidermal junction and ulceration represented overlapping criteria. CONCLUSION: Line-field confocal-OCT is a new promising technique that may support the non-invasive recognition of BSC through the simultaneous detection of BCC-associated and SCC-associated features. We hypothesize that the use of LC-OCT might be helpful not only in the diagnostic setting but also in the follow-up surveillance for an early identification of recurrences. Further larger studies are needed to prove this hypothesis.

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.

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.

Characterization of Basosquamous Cell Carcinoma: A Distinct Type of Keratinizing Tumour.

Basosquamous carcinoma is a rare clinical entity, which comprises 1.7-2.7% of all skin carcinomas. It is described as a basal cell carcinoma with features of squamous differentiation. To date, studies of the epidemiology of basosquamous carcinoma have been few and small in size. We report here the most extensive series of basosquamous carcinomas published to date, highlighting the differences between basosquamous carcinoma and other keratinizing tumours. Patients undergoing surgical excision for keratinizing tumours were enrolled in this study. Age, sex and tumour characteristics were recorded. A total of 1,519 squamous cell carcinomas, 288 basosquamous carcinomas and 4,235 basal cell carcinomas were collected. Basosquamous features were compared with those of basal cell and squamous cell carcinomas. For basosquamous carcinomas, 70.5% were located on the head and neck, particularly on the nose, forehead and cheeks, and represented almost 10% of the keratinizing tumours on the ears. Significant differences were found between basosquamous carcinoma and basal cell or squamous cell carcinomas. Basosquamous carcinoma should be considered a distinct type of keratinizing tumour with different anatomical, sex and age distributions.

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.

Postauricular Island Flap in Reconstruction of Auricula Tumor Defects.

The most common malignant tumor in humans is skin cancers. Skin cancers are most commonly seen in the head and neck region due to direct exposure to sunlight. Most frequently seen skin cancer in the auricula are basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). The aim of this study is to evaluate the results of postauricular island flap after resection of tumors in the auricula.Twelve patients aged 58 to 84 years were included in the study. Eight patients had BCC, 3 had SCC, and 1 had basosquamous carcinoma (BSC). The tumor was located at the cavum concha in 7 cases, antihelix in 3 cases, triangular fossa in 1 case and scapha in 1 case. Surgical procedure was performed under local anesthesia in 7 patients and under general anesthesia in 5 patients. Postauricular island flap was used in all cases. There were no early complications. Three patients had non-apparent narrowing of the auriculomastoid angle. The patients were followed for an average of 2.6 years between 1 and 9 years. Only one patient with basosquamous carcinoma of the cavum concha had recurrence at 19 months.We believe that the postauricular island flap may be a good alternative for the reconstruction of the defect after resection of tumors in the auricle due to its proximity to the surgical site, color matching, adequate thickness, good vascularization, aesthetic acceptance by the patient and completion of the procedure in one session.

Customized double-shell immobilization device combined with VMAT radiation treatment of basosquamous cell carcinoma of the scalp.

Malignancies with a superficial involvement of the scalp/skull present technical challenges for radiation-treatment-planning, such as achieving skin coverage with the prescribed dose and with the desirable conformity, homogeneity, and lower brain dose. We report a radiotherapy treatment technique for a patient diagnosed with diffuse basosquamous cell carcinoma of the scalp and adjacent skull-bone. This study presents the plan's quality parameters, patient's dosimetry, and patient's outcome. The patient was treated using volume-modulated-arc therapy (VMAT) and a double-shell-bolus full-head device (DSBFD) designed for patient immobilization and better skin coverage. A VMAT plan was generated using an Eclipse treatment-planning system for a prescribed dose of 60 Gy in 30 fractions. The treatment plan was analyzed to determine the conformity index (CI), the homogeneity index (HI), the target-coverage, and the dose to the organs-at-risk (OARs). Skin-doses were measured using optically stimulated luminescence (OSL) dosimeters. Clinical follow-up was performed by the radiation oncologist during and after the course of radiotherapy. With regard to planning target volume (PTV) coverage, the V95 was 99%. The measured and calculated dose to the skin was in the range 100-108% of the prescribed dose. The mean brain-PTV dose was 711 cGy. The CI and HI were 1.09 and 1.08, respectively. The mean positioning accuracy for the patient over the course of treatment was within 2 mm. The measured accumulated skin dose and planning dose was agreed within 2%. Clinical examination of the patient 6 months after radiotherapy showed good response to the treatment and a 90% reduction in scarring. The DSBFD technique combined with RapidArc treatment was useful in terms of the target dose distribution and coverage. Daily patient alignment was found very precise, reproducible and less time-consuming.

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.

Modernizing the Mohs Surgery Consultation: Instituting a Video Module for Improved Patient Education and Satisfaction.

BACKGROUND: Studies show that patients recall less than half of the information given by their physicians. Use of video in medicine increases patient comprehension and satisfaction and decreases anxiety. However, studies have not elaborated on video content. OBJECTIVE: To use principles of learning with multimedia to improve the Mohs surgery consultation. MATERIALS AND METHODS: The authors developed 2 informational videos on Mohs surgery: traditional versus narrative. The focus of the traditional video was purely didactic. The narrative video included patient testimonials, patient-physician interaction, and animations. New Mohs surgery patients viewed either the traditional (n = 40) or the narrative video (n = 40). Existing Mohs surgery patients (n = 40) viewed both videos. Both groups answered questionnaires about their satisfaction. RESULTS: For new Mohs surgery patients, no significant difference was found between the traditional and the narrative video groups because respondent satisfaction was high for both video formats. For existing Mohs surgery patients, all respondents (100%) reported that videos were helpful for understanding Mohs surgery; however, the majority would recommend the narrative over the traditional format (72.5% vs 27.5%, p = .01). CONCLUSION: Technology is useful for patient education because all patients preferred seeing a video to no video. Further research is needed to optimize effective multimedia use in patient education.

A custom positioning aid for an auricular prosthesis: A clinical report.

This report describes the treatment of a 68-year-old man with basosquamous cell carcinoma of the left auricular area. His oncologic treatment resulted in the loss of his left ear and much of the left temporal bone. The loss of a significant portion of the temporal bone precluded the use of extraoral implants. Owing to the lack of anatomic landmarks after his surgical treatment, positioning his auricular prosthesis proved challenging. The fabrication of his prosthesis and a custom positioning aid are described.

Perineural spread of basosquamous carcinoma to the orbit, cavernous sinus, and infratemporal fossa.

Basosquamous carcinoma is a rare, highly aggressive variant of basal cell carcinoma with elevated rates of recurrence, perineural invasion, and metastasis. We describe a patient who presented with unilateral complete ophthalmoplegia, ptosis, optic neuropathy, and trigeminal neuropathy due to perineural intracranial invasion of nasal basosquamous carcinoma via the sphenopalatine fossa to the cavernous sinus, orbit, and infratemporal fossa. To our knowledge, this is the first reported case of basosquamous carcinoma with perineural invasion involving the cavernous sinus in the English language ophthalmic literature. Physicians should be aware of the diagnostic features, clinical challenges and aggressive nature of basosquamous carcinoma, a rare diagnosis that can lead to significant morbidity/mortality when left unrecognized.

Basosquamous Carcinoma: Controversy, Advances, and Future Directions.

BACKGROUND: Basosquamous carcinoma is a rare cutaneous neoplasm that has caused considerable controversy as to its classification, pathogenesis, and management. OBJECTIVE: To review and summarize current literature on the definition, pathogenesis, incidence, and management of basosquamous carcinoma. MATERIALS AND METHODS: Through December 2015, an electronic search of the Pubmed database was performed using combinations of basosquamous carcinoma and metatypical basal cell carcinoma as search terms. RESULTS: A selection of 39 publications including case reports and series, retrospective studies, and systematic reviews of the literature were included. Descriptions of the definition of basosquamous carcinoma, clinical behavior, histopathological characteristics, current treatment therapies, and future advances are summarized. CONCLUSION: This systematic review provides a comprehensive overview of the current understanding of basosquamous carcinoma. Further study is required to elucidate the mechanisms driving the formation of this aggressive tumor.

Toll-Like Receptor 7 Staining in Malignant Epithelial Tumors.

BACKGROUND: As important players of the innate immune system, Toll-like receptors (TLRs) and their role for tumorigenesis have been in the focus of research. In particular TLR7 is an interesting candidate, as TLR7 agonists are broadly used for the treatment of cutaneous tumors. However, data addressing the baseline expression of TLR7 in both basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) on the protein level are lacking, while on the genomic level significantly elevated expression of TLR7 in SCC but not in BCC has been demonstrated. AIM: Our aim was to characterize the immunohistochemical staining pattern of TLR7 in SCC and BCC. Besides, we aimed to clarify if, in case of different TLR7 expression between SCC and BCC, TLR7 expression would help to define basosquamous carcinoma (BSC), a tumor entity sharing characteristics of both SCC and BCC. METHODS: We examined histopathological samples from 23 BCC, 4 BSC, and 24 SCC and characterized the expression of TLR7 by immunohistochemistry and immunofluorescence. RESULTS: We found that TLR7 was not expressed by the tumor tissue of SCC, BCC, and BSC, but by inflammatory cells located within the tumoral and/or peritumoral tissue. Whereas the overall expression of TLR7 did not differ between BCC and SCC (30.4% vs. 45.8%, respectively), we found that within the group of SCC, the well-differentiated SCC showed strong tumoral and/or peritumoral immunocellular TLR7 reactivity in contrast to the poorly differentiated SCC (73.33% vs. 11.1%, respectively). Besides, immunofluorescence double staining revealed the expression of TLR7 in immune cells closely interacting with T cells and natural killer cells. CONCLUSIONS: In contrast to genomic data, we did not find a general difference between baseline TLR7 expression of SCC and BCC on the protein level. Nevertheless, the expression of TLR7 by the inflammatory infiltrate associated with SCC may correlate with the degree of differentiation of SCC possibly indicating better outcome.