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.

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: 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.

[Long-term survival of a patient with stage IV basaloid squamous carcinoma of the esophagus with lung metastases following combined modality therapy].

A 72-year-old man visited our hospital because of dysphagia and weight loss. He was diagnosed by endoscopy with advanced (stage IV) basaloid squamous carcinoma of the thoracic esophagus. CT and CT-guided tumor biopsy revealed two lung metastases in the right upper and lower lobes, with diameters of 8 and 5 mm, respectively. The primary lesion disappeared after concurrent chemoradiotherapy consisting of 5-FU, cisplatin, and 60-Gy irradiation, which was administered for palliation of obstructive and hemorrhagic symptoms. Subsequently, eight cycles of chemotherapy were administered, resulting in a reduction in size of the metastases. However, multiple cycles of chemotherapy caused prolonged toxicity, and the metastases slightly enlarged during chemotherapy-free periods. Since the number of metastases did not change, stereotactic body radiotherapy was performed, which resulted in disappearance of the lung metastases. Five years following initial diagnosis, the patient has been doing well, with no signs of disease recurrence.

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.

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.

Prognostic significance of basaloid squamous cell carcinoma in head and neck cancer.

IMPORTANCE: Head and neck basaloid squamous cell carcinoma (BSCC) has been considered a more aggressive variant of squamous cell carcinoma (SCC) with a poorer prognosis, although case-control studies have reached conflicting conclusions. OBJECTIVE: To examine the prognostic significance of head and neck BSCC on overall survival in a large population-based registry. DESIGN AND SETTING: Retrospective data review of a population-based registry from the Surveillance, Epidemiology, and End Results database. PARTICIPANTS: Individual case data for 34,196 patients treated between January 2004 and December 2009 with head and neck primary SCC (n = 33,554) and BSCC (n = 642) of the oral cavity, oropharyx, larynx, or hypopharynx. Patients with metastatic disease, incomplete staging information, and those who did not receive surgery or radiation were excluded. INTERVENTIONS: Patients had been treated with surgery, radiation, or both. MAIN OUTCOMES AND MEASURES: Distribution of patient characteristics between patients of each histology. Hazard ratios, 3-year overall survival, subgroup, and multivariate analysis of patient and treatment characteristics were investigated. RESULTS: Across each cohort, patients with BSCC more often had high-grade tumors and treatment with lymph node dissection. Multivariate analysis found that group stage, T stage, N stage, size, lymph node dissection, and age statistically significantly influenced overall survival. In multivariate analysis, the hazard ratio for death for patients with BSCC in the oral cavity and larynx and hypopharynx was not statistically significantly different from that for SCC. In the oropharynx, the hazard ratio for death for BSCC histology compared with SCC histology was 0.73 (P = .03). CONCLUSIONS AND RELEVANCE: Compared with SCC, BSCC is not an independent adverse prognostic factor for patients with head and neck cancer. The Surveillance, Epidemiology, and End Results analysis has limits, including lack of information regarding chemotherapy, but after controlling for disease and treatment variables, including neck dissection and radiotherapy, BSCC histology did not have an independent adverse prognostic effect on overall survival. The reported association between human papillomavirus and BSCC histology may explain the lower hazard ratio for death in patients with oropharynx BSCC.

Clinical outcomes of basaloid squamous cell carcinoma of the esophagus: a retrospective analysis of 142 cases.

BACKGROUND: Basaloid squamous cell carcinoma of the esophagus (BSCCE) is a rare and distinctive tumor with no standard treatment. This study aimed to explore treatment in relation to prognosis of the disease. METHODS: A total of 142 patients with BSCCE that underwent treatment in our hospital from March 1999 to July 2010 were retrospectively analyzed. All patients received surgery, 42 postoperative radiotherapy and 28 patients chemotherapy. RESULTS: There were 26 patients included in stage I, 60 in stage II, 53 in stage III and 3 in stage IV. The clinical symptoms and macroscopic performances of BSCCE did not differ from those of typical esophageal squamous cell carcinoma. Among 118 patients receiving endoscopic biopsy, only 12 were diagnosed with BSCCE. The median survival time (MST) of the entire group was 32 months, with 1-, 3- and 5-year overall survival (OS) of 81.4%, 46.8% and 31.0%, respectively. The 5-year OS of stage I and II patients was significantly longer than that of stages III/IV, at 60.3%, 36.1% and 10.9%, respectively (p<0.001, p=0.001). The MST and 5-year OS were 59.0 months and 47.4% in patients with tumors located in the lower thoracic esophagus, and 27.0 months and 18.1% in those with lesions in the upper/middle esophagus (p=0.002). However, the survival was not significantly improved in patients undegoing adjunctive therapy. Multivariate analysis showed TNM stage and tumor location to be independent prognostic factors. Furthermore, distant metastasis was the most frequent failure pattern, with a median recurrence time of 10 months. CONCLUSION: BSCCE is an aggressive disease with rapid progression and a propensity for distant metastasis. It is difficult to make a definitive diagnosis via preoperative biopsy. Multidisciplinary therapy including radical esophagectomy with extended lymphadenectomy should be recommended, while the effectiveness of radiochemotherapy requires further validation for BSCCE.

New pathologic entities in penile carcinomas: an update of the 2004 world health organization classification.

Most primary malignant tumors of the penis are squamous cell carcinomas (SCC) of the usual type. In recent years several variants, each with distinctive clinicopathologic features, have been described. Pseudohyperplastic carcinoma and carcinoma cuniculatum are both low-grade, extremely well-differentiated SCC variants characterized by an indolent clinical course and good prognosis. The former, which may be confused with pseudoepitheliomatous hyperplasia, preferentially affects the inner foreskin mucosa of elderly men and the latter is a verruciform tumor with an endophytic, burrow-like pattern of growth. Pseudoglandular carcinoma (featuring solid tumor nests with extensive central acantholysis simulating glandular lumina) and clear cell carcinoma (human papillomavirus [HPV]-related tumors composed of periodic acid-Schiff positive clear cells) are aggressive tumors with a high incidence of inguinal nodal metastases. Papillary carcinomas are HPV-unrelated verruciform tumors composed of complex papillae with acanthosis, hyper- and parakeratosis, absence of koilocytes, irregular fibrovascular cores, and jagged tumor base. Finally, in warty-basaloid carcinomas areas of warty (condylomatous) and basaloid carcinomas coexist in the same tumor, either separated or intermingled, giving the tumor a variegated appearance. In this review special emphasis is given to the differential diagnosis of these special variants with a discussion of the possible implications for clinical management.

Basosquamous cell carcinoma in organ transplant patients: a clinicopathologic study.

BACKGROUND: Basosquamous cell carcinoma (BSCC) is a poorly known tumor showing pathological features of both basal and squamous cell carcinomas. BSCC has never been specifically studied in organ transplant recipients (OTRs). OBJECTIVE: We sought to study the clinicopathologic features of BSCC in OTRs and compare them with BSCC from nongrafted patients. METHODS: Tumors diagnosed as BSCC were re-evaluated pathologically and immunohistochemically for the expression of the human epithelial antigen to confirm the diagnosis. The clinicopathologic features of BSCC in OTRs were compared with 30 BSCC obtained from nongrafted patients. RESULTS: In our cohort of 3520 OTRs, 12 patients (0.34%) developed BSCC after a mean postgraft delay of 13.2 years, ie, later than other skin carcinomas. As compared with control patients, the age of OTRs with BSCC and the tumor thickness were significantly lower. BSCC were located on the head/neck in both groups in more than 75% of cases. No metastases developed in OTRs (mean follow-up 2.8 years). During the follow-up period (mean 16 years), OTRs with BSCC developed up to 220 additional premalignant and malignant skin tumors. After the diagnosis of BSCC, two patients developed lymph node metastasis of distinct squamous cell carcinoma. LIMITATIONS: This is a single-center, retrospective study. CONCLUSIONS: BSCC is a rare tumor, even in OTRs who are at high risk of carcinomas. Its incidence (0.34%) is comparable with that of cutaneous lymphomas and melanomas, and much lower than that of other nonmelanoma skin cancers. Contrary to previous reports, BSCC do not seem to behave more aggressively than other nonmelanoma skin cancers.

Metatypical carcinoma. A review of 327 cases.

INTRODUCTION: Metatypical cell carcinoma is a quite rare malignancy (5% of all non melanoma skin cancers), with features of basal cell carcinoma and squamous cell carcinoma. It is described as coexistence of basal cell carcinoma and squamous cell carcinoma with no transition zone between them. MATERIALS AND METHODS: We performed a retrospective study of 327 consecutive patients, diagnosed for metatypical carcinoma. Statistical analysis was made to determinate most affected areas, gender prevalence, average age, presence of ulceration and infiltration, peripheral clearance rate. RESULTS: A relevant difference came out between two genders. Chi-square test emphasized a relation between females and the presence of carcinoma on the scalp. In addition a strong correlation between mixed subtype and ulceration was evident. A strong relation between intermediate subtype and positive surgical margin was found; this data could identify a more aggressive behavior of intermediate type. DISCUSSION: Differently from melanoma that usually arises on sun exposed areas, no relation was found between sun exposion and this tumor. This characteristic stresses on the importance of other risks factor apart from sun exposition. CONCLUSIONS: We identify some correlation between our data that cannot be explained with previous interpretation of sun exposition.

Basaloid squamous cell carcinoma of the head and neck: report of 18 cases.

OBJECTIVE: To evaluate the clinical course and pathological characteristics of basaloid head and neck squamous cell carcinoma. METHOD: Retrospective study of 18 cases of basaloid head and neck squamous cell carcinoma. Epidemiological, clinical and histological data were analysed and the Kaplan-Meier test used to estimate survival rates. RESULTS: The majority of lesions were at an advanced stage. These lesions were primarily localised in the larynx, hypopharynx and oropharynx. Routine pre-therapeutic assessment of squamous cell carcinoma was performed. Pathological diagnosis was difficult, although immunostaining was extremely useful. Positive staining for KL1, MNF 116 and 34ßE12 and negative immunostaining for chromogranin and synaptophysin were also important factors in obtaining a definitive diagnosis. In the majority of cases, treatment involved surgery and radiotherapy. The five-year survival rate was 5 per cent. CONCLUSION: Basaloid squamous cell carcinoma is an uncommon head and neck lesion, with a challenging histological diagnosis. These lesions must be carefully monitored due to their aggressive course, and require multimodality treatment.

Basaloid squamous cell carcinoma: Report of five cases

Objectives: To document the clinical and histopathological characteristics of basaloid squamous cell carcinoma(BSCC). To add five new cases to the literature and compare them with another published series.Cases: retrospective review of five cases with the diagnosis of BSCC of the larynx. Results: all the patients weremale. They were heavy smokers and drinkers. Most of the tumours were supraglottic. Three patients presentedwith stage-IV disease and the other two with stage-I disease. Surgery supplemented with radiation was used inthree patients, partial surgery was used in another case and radiation and associated chemotherapy in the otherone. Eight neck dissections were performed, six of them were functional and the other two radical dissections.Two cases were found to have metastatic lymph nodes. There were not any distant metastases but two patients hadtumoral relapse.Conclusions: BSCC has well defined histological features. Central comedonecrosis within the cells nests, cell withnuclear palisading and high-grade dysplasia in overlaying mucosa are the main characteristics (AU)

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Carcinoma basoescamoso avançado de órbita: relato de caso / An advanced case of basosquamous carcinoma of the orbit: case report

Carcinoma basoescamoso é um tumor raro com características de tumor de células basais e escamosas interligados por uma área de transição. Tem sido descrito como um tumor agressivo com possibilidade de metástases à distância, o que difere substancialmente do carcinoma basocelular. Propomos neste relato a descrição de um caso de evolução crônica e das consequências do abandono do tratamento por causa do prognóstico reservado deste tipo de tumor de comportamento agressivo.

Basosquamous carcinoma is a rare tumor with features of both basal cell and squamous cell carcinoma, linked by a transition area. It is a rare epithelial neoplasm with a tendency for local recurrence. It also has a high incidence of distant metastasis, a condition that differentiates it from the basal cell carcinoma. In this case, the slow course of the infiltrative lesion associated to patient non-compliance to treatment led to a poor prognosis.

[Cutaneous basosquamous carcinoma]. / Carcinome basocellulaire métatypique.

INTRODUCTION: Basosquamous carcinoma is a rare entity that essentially affects the head and neck region in male patients. The authors present the clinical signs and progression as well as the therapeutic consequences of this disease through two observations. CASE REPORT 1: A 41-year-old man presented with basosquamous carcinoma of the right temporoparietal region treated initially with surgery alone. Five years later, he was operated on for a local and lymph node recurrence followed by radiation therapy, stabilizing the disease for 4 years; subsequently a second recurrence with metastasis to the chest area occurred. The patient died 10 years after the onset of his disease of diffuse pneumopathy with severe septicemia. CASE REPORT 2: A 71-year-old man presented retroauricular basosquamous carcinoma at first treated with wide resection, but the surgical limits were invaded. He developed local recurrences treated with surgical resection until total petrosectomy, but the surgical limits were always invaded. Radiotherapy was delivered. Seven years after the end of treatment, he developed a local recurrence invading the brain, which was deemed untreatable. DISCUSSION: Basosquamous carcinoma is characterized by its severe aggression and its tendency to recur. Treatment is essentially surgical. Radiotherapy is an adjuvant for the cases with high risk of recurrence. The role of chemotherapy is not yet proved.

Basosquamous carcinoma.

BACKGROUND: Basosquamous carcinoma is considered an aggressive type of basal cell carcinoma (BCC) with an increased risk of recurrence and metastases. This concept has been perpetuated in the literature in spite of confusing terminology, limited scientific data, and the contradictory surgical experiences of some observers. METHODS: This is a narrative review based on a MEDLINE search of articles in English and a manual search of popular dermatology textbooks to define basosquamous carcinoma, its incidence, clinical behavior, and treatment of choice. RESULTS: There are no specific clinical features to distinguish basosquamous carcinoma from other BCC types and the diagnosis is made only after biopsy. There are several histologic definitions of basosquamous carcinoma ranging from a characteristic combination of BCC and squamous cell carcinoma with or without a transition zone, to any BCC with evidence of keratinization. The authors confine the use of the term to an infiltrative growth BCC with areas of keratinization and/or intercellular bridge formation in the setting of a prototypic proliferative stromal reaction. The term "metatypical basal cell carcinoma" is considered a synonym but its use is discouraged for the reasons outlined. The reported incidence of basosquamous carcinoma ranges from 1.2% to 2.7%. Published recurrence rates are 12% to 51% for surgical excision and 4% for Mohs micrographic surgery. The incidence of metastasis is at least 5%. The aggressive biological behavior and clinical course distinguish basosquamous carcinoma from other forms of BCC. LIMITATIONS: This study is a literature review, contains a limited number of patients, and is mostly retrospective studies. CONCLUSION: The terminology surrounding basosquamous carcinoma is confusing and there is a need for more uniform language. Based on our review and personal experience, we propose a more precise and specific definition. Data regarding the incidence, recurrence, and metastasis rates of basosquamous carcinoma are based mostly on retrospective series with a limited number of cases. We conclude that although the incidence of basosquamous carcinoma is unknown, there is a literature precedent suggesting more aggressive biological behavior. We believe that complete surgical excision is the preferred approach, and that basosquamous carcinoma is an ideal candidate lesion for Mohs micrographic surgery.

[An advanced case of basosquamous carcinoma of the orbit: case report]. / Carcinoma basoescamoso avançado de órbita: relato de caso.

Basosquamous carcinoma is a rare tumor with features of both basal cell and squamous cell carcinoma, linked by a transition area. It is a rare epithelial neoplasm with a tendency for local recurrence. It also has a high incidence of distant metastasis, a condition that differentiates it from the basal cell carcinoma. In this case, the slow course of the infiltrative lesion associated to patient non-compliance to treatment led to a poor prognosis.

[Diagnosis and treatment of basaloid squamous cell carcinoma of the esophagus].

OBJECTIVE: To investigate the histopathological features of basaloid squamous cell carcinoma of the esophagus, and to explore the ways of its diagnosis, differential diagnosis and treatment. METHODS: The clinical data and pathological features of 23 cases of esophageal basaloid squamous cell carcinoma were reviewed and analyzed retrospectively. RESULTS: The tumors were mainly located at the middle third segment of the esophagus. The 1-,2- and 3-year survival rates were 60.9%, 21.7% and 0, respectively. CONCLUSION: The basaloid squamous cell carcinoma of the esophagus is highly malignant with poor prognosis. Radical resection combined with radiotherapy and chemotherapy is required.