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.

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.

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.

Utility of Ber-EP4 and MOC-31 in Basaloid Skin Tumor Detection.

Ber-EP4 has been the traditional immunostain used for the detection of basaloid skin tumors. Recently, MOC-31 has shown be superior to Ber-EP4 in the detection of basosquamous basal cell carcinoma (BCC) and many centers are now using both Ber-EP4 and MOC-31 antibodies together to detect these lesions. The objective of this study was to compare the utility of using both Ber-EP4 and MOC-31 immunostains in the detection of basaloid skin tumors and to better characterize the previously unknown staining properties of MOC-31 in cutaneous lesions. To do this, 76 basaloid skin tumors stained with both Ber-EP4 and MOC-31 were obtained. Diagnoses included basosquamous BCC, Merkel cell carcinoma, adenoid cystic carcinoma, microcystic adnexal carcinoma, sebaceous carcinoma, trichoepithelioma, trichoblastoma, sebaceous adenoma, sebaceoma, and follicular induction overlying dermatofibroma. The distribution and intensity of Ber-EP4 and MOC-31 staining in these lesions was scored. These scores were analyzed using a truth table, χ test, and Pearson correlation tests. The overall mean and SD of the scores were also obtained. Overall, we found Ber-EP4 and MOC-31 to be statistically equivalent immunostains for the diagnosis of basaloid skin tumors. We recommend the use of only one of these antibodies and favor MOC-31 for the detection of basaloid skin tumors. We also describe MOC-31 staining properties in different cutaneous lesions.

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.

Basosquamous carcinoma: Dermoscopic clues to diagnosis.

Basosquamous carcinoma (BSC) is a rare skin cancer which has areas of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) and a transition zone between them. However, dermoscopic features of BSC are not well described in the published work, except one study. The aim of the present study was to better identify and clarify the dermoscopic findings of BSC in the largest group of patients in the published work and to describe its dermoscopic features according to histopathologically BCC-dominant, SCC-dominant and intermediate categories. Dermoscopic features of 36 histopathologically proven BSC and their dermatopathological correlates were retrospectively analyzed. Dermoscopic features were evaluated by pattern analysis. Keratin mass (91.7%) was the most common dermoscopic feature. Surface scaling (77.8%), ulceration (69.4%), white structureless areas (69.4%), white clods (66.7%) and blood spots on keratin mass (66.7%) were the other frequent findings. Polymorphous vascular pattern consisting of various combinations of branched, serpentine, straight, coiled or looped vessels were detected in 61% of the lesions. BSC has BCC-dominant vascular features together with otherwise SCC-dominant morphology, the common pattern seen in BSC lesions being BCC-dominant polymorphous or monomorphous vasculature, together with dermoscopic findings of keratinization. White circles, known to be a valuable clue to SCC and keratoacanthoma, were present at the same magnitude in BSC in our study. The observed histological correlation of eosinophilic keratin overlying the epithelium which lined follicular infundibulae in these tumors, provides a plausible new perspective on dermoscopic white circles.

[The role of dermoscopy in the diagnosis of basosquamous carcinoma]. / L'apport de la dermoscopie dans le carcinome basosquameux.

Basosquamous carcinoma (BSC) is a rare skin cancer which has areas of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) and a transition zone between them. However, dermoscopic features of BSC are not well described in the literature, except for two studies. The aim of this case study was to better identify and clarify the role of dermoscopy in the diagnosis of BSC, although histological confirmation is necessary.

Basosquamous carcinoma of the head and neck: clinical and histologic characteristics and their impact on disease progression.

OBJECTIVES: Basosquamous carcinoma (BSC) is a rare tumor entity, and the most common onset is in the head and neck region (BSC-HN). The data on diagnosis, treatment, and especially risk assessment concerning disease course and outcome are deficient or inconsistent. This study aimed to evaluate risk factors for local relapse (LR) and lymph node metastasis (LNM) and their impact on progression-free survival (PFS). MATERIALS AND METHODS: In a retrospective monocentric study, patients with BSC-HN treated between 1999 and 2011 were analyzed regarding clinical and histologic characteristics. Prognostic parameters for LR, LNM, and PFS were evaluated. In total, 89 patients (55 male, 34 female, mean age of 71.8 years) with a mean follow-up time of 47.7 months (range 12-112) were included. RESULTS: LR occurred in four patients (4.5%), LNM occurred in five patients (5.6%). Patients with LNM had a significantly shorter PFS time (16.1 months) compared with patients without LNM (154.2 months; P < .001). Tumor depth and size (T classification), incomplete resection, localization at the ear, deep maximal vertical infiltration, muscle and vessel invasion all showed significant (P < .05) associations with LR, LNM, and shorter PFS time. BSC showed more histologic features of basal cell carcinoma (BCC), especially with regard to BerEP4 expression. CONCLUSION: While histology shows some typical characteristics of BCC, the biologic behavior and aggressiveness of BSC are similar to those of cutaneous squamous cell carcinoma. This is the first study to show that LR and, especially, LNM indicate a higher risk of an unfavorable outcome.

Relapsing advanced metatypical basal cell carcinomas (MTBCC) of the face: surgical modalities.

Metatypical basal cell carcinoma (MTBCC) represents a high-risk type of cutaneous tumour. We report about three different patients with relapsing advanced large MTBCC: one of the scalp and two of the cheek region. Such patients required in most of the cases a complex surgical approach to achieve a stable and complete remission. In the first presented patient a combination of flaps and grafts has been performed. We describe tailored surgical approaches. By this contrivance it is possible to treat even elderly patients with exposed bone after complete excision effectively and safe. Interdisciplinary team work is for the benefit of these patients.

Basaloid squamous cell carcinoma of the oropharynx: comparison of two cases and review of the literature.

We describe a rare case of BSCC in the retromolar trigone with only 3 other cases in the literature and also compare the differences between 2 cases of BSCC in terms of presentation and progression. The first patient had a markedly slower progression with painful retromolar trigone swelling over 4 months without nodal metastases. In contrast, the second patient gave a 2-week history of neck swelling with nodal involvement, indicating extremely rapid progression. Our management was tailored accordingly with the first patient undergoing intraoral excision of tumour and adjuvant radiotherapy while the other had bilateral neck dissection with postoperative chemoradiotherapy. Both patients achieved good outcome and are free from disease.

Bilateral lower eyelid basosquamous cell carcinoma: a rare case.

Basosquamous cell carcinoma is a subtype of basal cell cancer. It is known to be more aggressive than basal cell cancer. A 70-year-old male patient was admitted to our clinic for evaluation of cosmetic problems caused by masses on both lower eyelids for at least two years. The mass excision from and reconstruction of lower eyelids were performed. Histopathological examination of the resected masses was consistent with basosquamous cell carcinoma. We present a case of basosquamous cell carcinoma involving bilateral lower eyelids with a different clinical appearance. To the best of our knowledge, this is the first report of bilateral basosquamous cell carcinoma in a patient.

Basaloid squamous cell carcinoma of the oral cavity: an analysis of 92 cases.

OBJECTIVES/HYPOTHESIS: Basaloid squamous cell carcinoma (BSCC) is considered a rare and possibly more aggressive squamous cell carcinoma (SCC) variant. Until now, a series of exclusively oral cavity BSCC patients has not been previously reported. We endeavored to compare BSCC and SCC of the oral cavity, focusing on epidemiologic factors and survival outcomes. STUDY DESIGN: Retrospective analysis of population-based data. METHODS: We compared epidemiologic factors, clinicopathologic data, and disease-specific survivals (DSS) between 92 patients with oral cavity BSCC and 15,181 patients with SCC. RESULTS: High-grade tumors and distant metastases were more common in the BSCC group (P≤0.001). On multivariable analysis controlling for disease stage, BSCC patients had similar DSS to those with typical SCC (P=0.231). Although there was a trend favoring definitive radiotherapy for BSCC, there were no significant differences in treatment approach between BSCC and SCC. The choice of treatment modality (radiation, surgery±radiation) did not reveal a difference in DSS between the two tumor subtypes. CONCLUSION: Analysis of the largest oral cavity BSCC series to date demonstrates that BSCC of the oral cavity carries a comparable prognosis to conventional-type oral SCC. LEVEL OF EVIDENCE: 2b.

Transglottic basaloid squamous cell carcinoma of the larynx.

OBJECTIVE: To report a rare case of Transglottic Basaloid Squamous cell carcinoma of the larynx and review the pathologic features of these lesions. CASE REPORT: A 64 year old male, heavy smoker and alcohol abuser, presented with a 6 month history of hoarseness. Laryngoscopy revealed a right transglottic lesion involving the epiglottis, aryepiglottic fold, ventricle and true vocal fold. Microscopically, the tumor was characterized by infiltrating solid sheets of basaloid cells showing palisading pattern along the edges. In areas of solid growth, tumor cells displayed scant cytoplasm, and hyperchromatic nuclei. A portion of the tumor abutting the thyroid cartilage showed squamous differentiation. An island of tumor cells with comedonecrosis was also noted. Immunohistochemical staining for a number of markers was performed. CONCLUSION: Basaloid squamous cell carcinoma displays a biphasic histology. The stage of the disease at presentation is invariably advanced with metastatic lymphadenopathy in two thirds of the patients.

[Fluorescence diagnosis of non-melanoma skin cancer]. / Hámeredetu bordaganatok fluoreszcens diagnosztikája.

Photodynamic therapy involves - in dermatological practice usually exogenous - application of a photosensitizer then activation of accumulated protoporphyrin IX by light with an appropriate wavelength after a short incubation period. It is an evidence based method to treat certain non-melanoma skin cancers. During treatment when the excited protoporphyrin IX returns to base state, reactive oxygen species are formed leading to cell death in rapidly proliferating cells. Fluorescence of excited protoporphyrin IX can be used in diagnostics as well. In ultraviolet light, the photodamaged or neoplastic areas show coral red fluorescence which can clearly be distinguished from the much lower fluorescence of adjacent normal tissue. This process is suitable for exact determination of tumor margins so it can be used for planning surgical procedures or after photodynamic therapy at a follow up visit for the visualization of the therapeutic result. The present article reviews the literature of photodynamic diagnosis that is also used by the authors.

Diagnostic problems in precancerous lesions and invasive carcinomas of the penis.

Penile precancerous and invasive lesions exhibit a variegated morphology. Although the diagnosis and classification of penile tumors is straightforward in most cases, a few entities are problematic, especially to pathologists from countries in which penile cancer is rarely encountered. The differential diagnosis of squamous hyperplasias from differentiated penile intraepithelial neoplasia or from extremely low-grade invasive neoplasms (eg, pseudohyperplastic and verrucous carcinomas) may be particularly difficult. Similarly, given the morphologic features shared by all verruciform tumors (ie, verrucous, warty, papillary, and cuniculatum carcinomas, along with giant condylomas), it is challenging at times to distinguish one from another. At the other end of the spectrum, because of their lack of differentiation, it is sometimes difficult to classify high-grade carcinomas, such as basaloid and sarcomatoid, which may have etiologic/prognostic implications. Penile mixed tumors, harboring more than 1 histologic subtype and grade, constitute a frequent finding in routine pathology. The recognition of distinctive morphologic patterns and histologic grades in these tumors is important because these features could be related to etiologic factors, such as human papillomavirus infection, or they could influence outcome. Penile tumors with glandular features (eg, adenosquamous and mucoepidermoid carcinomas), although rare, may be confused with the more common pseudoglandular (adenoid, acantholytic) variant of squamous cell carcinomas, their main mimicker. In this review we provide clues that may help in the differential diagnosis of these lesions.

Validation of claims data algorithms to identify nonmelanoma skin cancer.

Health maintenance organization (HMO) administrative databases have been used as sampling frames for ascertaining nonmelanoma skin cancer (NMSC). However, because of the lack of tumor registry information on these cancers, these ascertainment methods have not been previously validated. NMSC cases arising from patients served by a staff model medical group and diagnosed between 1 January 2007 and 31 December 2008 were identified from claims data using three ascertainment strategies. These claims data cases were then compared with NMSC identified using natural language processing (NLP) of electronic pathology reports (EPRs), and sensitivity, specificity, positive and negative predictive values were calculated. Comparison of claims data-ascertained cases with the NLP demonstrated sensitivities ranging from 48 to 65% and specificities from 85 to 98%, with ICD-9-CM ascertainment demonstrating the highest case sensitivity, although the lowest specificity. HMO health plan claims data had a higher specificity than all-payer claims data. A comparison of EPR and clinic log registry cases showed a sensitivity of 98% and a specificity of 99%. Validation of administrative data to ascertain NMSC demonstrates respectable sensitivity and specificity, although NLP ascertainment was superior. There is a substantial difference in cases identified by NLP compared with claims data, suggesting that formal surveillance efforts should be considered.