Conventional Squamous Cell Carcinoma Research Articles

Clinicopathologic and Molecular Characterization of High-Risk Human Papillomavirus-Positive Carcinomas of the Urinary Tract.

Human papillomavirus (HPV) is a well-known cause of squamous cell carcinomas of anogenital and oropharyngeal regions, where treatment strategies and prognosis depend on HPV status. The significance of HPV status in tumors arising along the urinary tract is not well established. To provide detailed clinical, morphologic, immunohistochemical, and molecular analysis of HPV+ urinary tract carcinomas (UTCs). We identified and retrospectively examined 12 HPV+ UTCs, confirmed by high-risk HPV in situ hybridization. The HPV+ UTCs originated from the urethra (9) and urinary bladder (3); 5 of 12 (42%) presented with nodal metastasis. On morphology, HPV+ UTCs were predominantly basaloid; well-differentiated squamous areas were focally seen. Available immunohistochemistry (IHC) showed strong staining for p16 (11 of 11), p63 (12 of 12), cytokeratin (CK) 903 (11 of 11), and CK5/6 (11 of 11); variable staining for GATA3 (8 of 12) and CK7 (4 of 11); and rare uroplakin II staining (1 of 12). Molecular analysis revealed the most frequently altered genes: KMT2C (42%), PIK3CA (42%), and KMT2D (25%). In contrast to published conventional urothelial and squamous cell carcinoma molecular data, TERTp mutation was rare (8%), and no TP53 or CDKN2A aberrations were identified. During available follow-up (11 of 12; median, 39 months), 6 patients required treatment for recurrence; ultimately, 1 died of disease, 2 were alive with disease, and 8 had no evidence of disease. Finally, we provide 11 HPV- squamous predominant UTCs for IHC and molecular comparisons; notably, a subset of HPV- UTCs was positive for p16 IHC (27%), making p16 IHC a less-specific surrogate marker for HPV status at this site. HPV+ UTCs show distinct clinical, morphologic, and molecular characteristics, suggesting important roles for HPV in UTC.

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.

[Clinicopathological and molecular characteristics of esophageal carcinoma with ductal differentiation: analysis of 17 cases].

Objective: To investigate the clinicopathological features and molecular genetic characteristics of esophageal carcinoma with ductal differentiation, and to summarize the experiences in its diagnosis and treatment. Methods: A total of 17 cases of esophageal carcinoma with ductal differentiation diagnosed in Ningbo Clinical Pathological Diagnosis Center, Ningbo, China from June 2011 to December 2022 were collected. The clinical information and pathological diagnosis was reviewed. The tumor histological features and immunohistochemical results were analyzed. The next-generation sequencing was performed to detect and analyze the gene mutations in tumor samples. Results: The 17 patients included in this study were 54-77 years old, with a median age of 66 years. There were 16 males and 1 female. Among them, 9 cases were mainly carcinoma with ductal differentiation. The squamous epithelium on the tumor's surface was accompanied by high-grade intraepithelial neoplasia. The tumor and atypical squamous epithelium were transitional, and the focus was accompanied by various proportions of squamous cell carcinoma component (less than 10%). The other 8 cases were mostly squamous cell carcinoma, basaloid squamous cell carcinoma or sarcomatoid carcinoma with various degrees of tumor specific differentiation and focal area of carcinoma with ductal differentiation (less than 10%). The tumor cells in the area with ductal differentiation were mainly arranged in small tubes, while the tubes showed a double-layer structure, including the inner cells and outer cells of the lumen. Immunohistochemical results showed that the outer cells of the tumorous tubules expressed p63, p40, CK5/6 and CK34βE12, while the inner cells expressed CK7. Compared with esophageal squamous cell carcinoma reported in the literature, the frequency of gene mutations such as MYC (P=0.002), TP63 (P=0.002), CDKN1C (P=0.002) and NFE2L2 (P=0.045) was significantly lower in this group of cases. At the signaling pathway level, the mutation frequency of NOTCH signaling pathway (P=0.041) was significantly higher, while the mutation frequencies of NRF2 pathway (P=0.013) and PI3K pathway (P=0.009) were significantly lower than that of esophageal squamous cell carcinoma. Conclusion: Esophageal carcinoma with ductal differentiation is a type of esophageal carcinoma with unique morphology, and its molecular changes are also significantly different from those of conventional esophageal squamous cell carcinoma.

Granulation tissue-like spindle cell (sarcomatoid) carcinoma of the head and neck: a deceptively bland-looking underdiagnosed malignancy.

The diagnosis of head and neck spindle cell squamous carcinoma (SC-SCC) is often challenging. Lesions with a prominent inflammatory infiltrate and reactive vessels may have a granulation tissue-like appearance, therefore being difficult to distinguish from reactive lesions, like contact ulcers, post-intubation granulomas, inflammatory pseudotumors, or benign vascular lesions. In this study, we analyzed the clinicopathological features of a series of 17 head and neck SC-SCC with granulation tissue-like appearance. All patients, but two, were males, ranging in age between 57 and 80years. The larynx was the most frequently affected site (n = 12), followed by the tongue (n = 4). One tumor was hypopharyngeal. Most consult cases were submitted with benign suggestion or because of unexpected recurrences of granulation tissue polyps. Histologically, all lesions consisted of an ulcerated polypoid proliferation of moderately to markedly atypical spindle cells, with a minor component of conventional invasive or in situ squamous carcinoma. At least one cytokeratin cocktail was positive in 13 cases. The staining was limited to a few neoplastic cells in most cases. Positivity for p63, p40, and cytokeratins 5/6 was detected only in the conventional squamous cell carcinoma component, when present. ALK1 was negative in all cases. Sixteen cases were tested for p53 and all showed aberrant expression (12 diffusely positive and 4 of null-phenotype). The diagnosis of granulation tissue-like SC-SCC is challenging due to the close clinical and histological overlap with several benign conditions. Since the expression of epithelial markers is limited, the use of an immunohistochemical panel including p53 is recommended.

Papillary Variant of Oral Squamous Cell Carcinoma of Alveolar Mucosa- A Case Report and Review

Papillary Squamous Cell Carcinoma (PSCC) is a less frequent subtype of Squamous Cell Carcinoma (SCC) with a more favorable prognosis compared to conventional oral squamous cell carcinoma. PSCC has a distinctive exophytic and papillary projection. The upper aerodigestive tract is the most commonly affected site with a higher incidence of occurrence in the larynx. The papillary variant of oral squamous cell carcinoma involving gingiva or alveolar ridge is relatively uncommon and less reported. Other differential diagnosis of papillary gingival masses is reactive gingival lesions and fungal infections. An accurate diagnosis is vital for both therapeutic and prognostic purposes. This article describes the case of papillary variant oral squamous cell carcinoma in a 75-year-old male in the maxillary alveolar region depicting histopathological features of exophytic growth with hyperplastic stratified squamous epithelium with basaloid cells invading the underlying connective tissue.

Ovarian squamous cell carcinoma associated with teratoma: a report of six cases with genomic analysis

Ovarian squamous cell carcinoma (SCC), particularly the sarcomatoid variant, arising from teratoma is a rare malignant tumour with unfavourable clinical outcomes. Its molecular genetic alterations have not been well-documented to date. This study aims to characterise the molecular features and to provide potential therapeutic targets in this rare entity. We analysed the clinicopathological and immunohistochemical features of six primary ovarian SCC. These cases were subject to targeted next-generation sequencing to detect genomic features. We found that all six ovarian SCC (four conventional and two sarcomatoid SCC) were associated with mature cystic teratomas. Patient 3 (FIGO stage IIIa) and Patient 4 (stage IIb) died of disease at 10 and 11 months, respectively. The remaining patients (three with stage I and one with IIc) including the two with sarcomatoid SCC, were alive with no evidence of disease at 28-72 months. All patients showed PD-L1 expression (tumour proportion score: range 10-78%, median 41%; combined positive score: range 12-85, median 42) and a high tumour mutation burden (range 13.4-25.7 mutations/Mb, median 16.5). The most frequently recurrent mutations included PIK3CA (4/6), TP53 (4/6), TERT promoter (4/6), CDKN2A (3/6). Mutations in homologous recombination repair pathway genes (BLM, ATM, BRCA1, BRIP1 and ATM) were found in 5/6 patients. The sarcomatoid SCC shared a similar mutational profile with conventional SCC, and no recurrent genetic mutations exclusively in sarcomatoid SCC were identified. Our study suggests the potential benefits of immune checkpoint inhibitors and/or PARP inhibitors in patients with primary ovarian SCC on account of PD-L1 expression and genomic features. Ovarian sarcomatoid SCC may be clonally related to the conventional SCC. A multiple-institutional, clinical and molecular study will consolidate these findings in the future.

Whitish Patch over Soft Palate: A Case Report of Incidental Finding of Basaloid Squamous Cell Carcinoma

Abstract. Introduction: Whitish lesion over the oropharyngeal mucosal lesion is traditionally attributed to benign lesions such as leukoplakia, oral candidiasis or lichen planus, which can be diagnosed through histopathological examination. Yet, performing a biopsy is prudent in all cases of persistent whitish lesions to rule out a more sinister pathology such as malignancy. Herein, we report an incidental finding of a whitish lesion in the soft palate of a gentleman who presented with otalgia and otorrhea, which turned out to be basaloid squamous cell carcinoma (BSCC). Therefore, we highlight the importance of thorough, meticulous and complete Ear, Nose and Throat examinations in all patients as they enable early diagnosis of a sinister pathology in this patient. Keywords: Basaloid squamous cell carcinoma, Conventional squamous cell carcinoma  Immunohistochemisrty, Squamous cell carcinoma, Soft palate; Oropharyngeal carcinoma

CONVENTIONAL SQUAMOUS CELL CARCINOMA COEXISTING WITH A VERRUCOUS CARCINOMA: A HYBRID NEOPLASM

Verrucous carcinoma (VC) is a low-grade variant of squamous cell carcinoma (SCC) that lacks the cytological features of malignancy and does not metastasize, differently from the conventional SCC. Oral hybrid verrucous carcinoma is a rare neoplasm comprised of VC and conventional SCC. This study presents a case report of this hybrid neoplasm in an 81-year-old male former smoker. In the intraoral examination, the patient exhibited a white lesion with a verrucous surface in the maxillary alveolar ridge. Under clinical hypothesis of VC or conventional SCC, an incisional biopsy was performed. Microscopically, the tumor showed an endophytic proliferation of hyperkeratinized squamous epithelium with parakeratin plugging and bulbous rete ridges extending in depth. Areas of infiltration by trabeculae and islands of well-differentiated SCC were also observed. The final diagnosis was SCC coexisting with a hybrid verrucous carcinoma (VC). The patient was referred to a head and neck service and is undergoing treatment. Verrucous carcinoma (VC) is a low-grade variant of squamous cell carcinoma (SCC) that lacks the cytological features of malignancy and does not metastasize, differently from the conventional SCC. Oral hybrid verrucous carcinoma is a rare neoplasm comprised of VC and conventional SCC. This study presents a case report of this hybrid neoplasm in an 81-year-old male former smoker. In the intraoral examination, the patient exhibited a white lesion with a verrucous surface in the maxillary alveolar ridge. Under clinical hypothesis of VC or conventional SCC, an incisional biopsy was performed. Microscopically, the tumor showed an endophytic proliferation of hyperkeratinized squamous epithelium with parakeratin plugging and bulbous rete ridges extending in depth. Areas of infiltration by trabeculae and islands of well-differentiated SCC were also observed. The final diagnosis was SCC coexisting with a hybrid verrucous carcinoma (VC). The patient was referred to a head and neck service and is undergoing treatment.

THE ROLE OF DENTISTRY IN THE EARLY DIAGNOSIS AND FOLLOW-UP OF POTENTIALLY MALIGNANT DISORDERS: A CASE REPORT

In 2017, a 66-year-old male patient, smoker and alcohol-addicted for the last 52 years, presented a white plaque with a diagnosis of epithelial hyperplasia with papillomatosis and mild epithelial dysplasia. The patient did not continue with follow-up care. Later, in May 2021, he returned for further exams, presenting an extensive, hard, ulcerated exophytic erythroleukoplakia, with undefined limits on the edge of the tongue. New biopsies were performed, and the anatomopathological examination showed moderately epithelial dysplasia in the soft palate region. The left tongue was diagnosed with moderately differentiated conventional squamous cell carcinoma staging cT3acN1cM0 tongue squamous cell carcinoma. Treatment consisted of left partial glossectomy, together with radiotherapy (20 fractions x 250cGy/field). These findings are important because they imply that many patients with oral premalignant lesions are not diagnosed in a timely manner. thereby failing to receive the benefits of early detection. In 2017, a 66-year-old male patient, smoker and alcohol-addicted for the last 52 years, presented a white plaque with a diagnosis of epithelial hyperplasia with papillomatosis and mild epithelial dysplasia. The patient did not continue with follow-up care. Later, in May 2021, he returned for further exams, presenting an extensive, hard, ulcerated exophytic erythroleukoplakia, with undefined limits on the edge of the tongue. New biopsies were performed, and the anatomopathological examination showed moderately epithelial dysplasia in the soft palate region. The left tongue was diagnosed with moderately differentiated conventional squamous cell carcinoma staging cT3acN1cM0 tongue squamous cell carcinoma. Treatment consisted of left partial glossectomy, together with radiotherapy (20 fractions x 250cGy/field). These findings are important because they imply that many patients with oral premalignant lesions are not diagnosed in a timely manner. thereby failing to receive the benefits of early detection.

Atypical Squamous Verrucous Lesions of the Oral Cavity: Challenges in Interpretation of Small Incisional Biopsies.

Squamous verrucous proliferative lesions of oral cavity can pose a diagnostic challenge for the general pathologist, especially on small biopsies. The superficial nature of incisional biopsies and inconsistent histologic terminologies used for these lesions contribute to often-discrepant clinical diagnosis, resulting in delayed treatment.This study aims to explore the proliferative squamous lesions of oral cavity, correlate biopsy & resection diagnoses, and evaluate possible reasons for discrepant diagnosis (if any). A retrospective review of oral verrucous squamous lesions was undertaken. Pathology database was searched for oral cavity biopsies from January2018 through August2022 with the keywords: atypical, verrucous, squamous, and proliferative. Cases with follow-up were included in this study. A blinded review of the biopsy slides was performed and documented by a single head and neck pathologist. Demographic data, biopsy and final diagnosis were recorded. Twenty-three cases met criteria for inclusion. The mean patient age was 61.1years with a male: female ratio of 1.09. Most frequent site was lateral border of tongue (36%) followed by buccal mucosa and retromolar trigone. The most common biopsy diagnosis was "Atypical squamoproliferative lesion, excision recommended" (n = 16/23, 69%) with 13/16 showing conventional squamous cell carcinoma (SCC) on follow-up resection. 2/16 atypical cases underwent repeat biopsy for confirmation of diagnosis. Overall, conventional SCC was the most prevalent final diagnosis (73%, n = 17), followed by verrucous carcinoma (17%, n = 4). On slide review, six initial biopsies were reclassified as SCC, while one final diagnosis was reclassified as a hybrid carcinoma (on resection specimen). Diagnostic concordance (biopsy and resection) was observed in three cases, all three were recurrences. The primary reasons for discrepant diagnosis on initial biopsies were found to be 1. Obscuring inflammation, 2. Superficial biopsies, and 3. Under recognition of morphologic features (e.g., tear shaped rete, loss of polarity, dyskeratotic cells, paradoxical maturation) that help differentiate dysplasia from reactive atypia. This study highlights the rampant interobserver variability in diagnosis of oral cavity squamous lesions and emphasizes importance of identifying morphologic clues that can aid in correct diagnosis, thereby helping in adequate clinical management.

Cancers rares de la tête et du cou sous l’égide du REFCOR, partie 2

Among the 16,000 new cases of malignant tumors of the head and neck diagnosed in France each year, 10% are not conventional squamous cell carcinomas. These so-called rare cancers are distinguished by their presentation and patterns of failure, which is important to recognize in order to offer specific adapted management and maximize the chances of tumor control. These cancers can be rare by their histology as well as their anatomical location when arising from the paranasal sinuses, salivary glands and ear. The management of these heterogeneous rare diseases of complex treatment has considerably been structured over the last 15years, in particular via the French ENT Cancer Expertise Network (REFCOR) and international networks and registries (EURACAN, etc.). Structuration also favors research with identification of new entities and setting up of specific therapeutic trials. A first article (part 1) discusses the diagnostic and therapeutic specificities of these rare cancers, and develops the recommendations of the REFCOR concerning rare epithelial tumors, i.e., salivary tumors, sinonasal tumors, variants of conventional squamous cell carcinomas, neuroendocrine carcinomas, malignant odontogenic tumors, and ear tumors. This second article (part 2) is focused on non-epithelial tumors (sarcomas, mucosal melanomas, lymphomas, tumors of uncertain or undetermined malignancy) and describes the organization and missions of the REFCOR.

Cancers rares de la tête et du cou sous l’égide du REFCOR, partie 1

Among the 16,000 new cases of malignant tumors of the head and neck diagnosed in France each year, 10% are not conventional squamous cell carcinomas. These so-called rare cancers are distinguished by their presentation and patterns of failure, which is important to recognize in order to offer specific adapted management and maximize the chances of tumor control. These cancers can be rare by their histology, which determines their local invasiveness, and their hematogenous/nodal spread. Their diagnosis can be difficult and often requires comprehensive immunohistochemistry and genomic techniques. Expert pathology review is recommended in the cases of undifferentiated tumors, sarcomas and at the slightest diagnostic doubt. These rare cancers can also be rare by their anatomical location when arising from the paranasal sinuses, salivary glands and ear. Their location requires knowledge of their specific extension routes, and may call for a specific surgical technique (skull base endoscopic sinus surgery, extended total parotidectomy, etc.) and adapted radiotherapy to spare healthy organs surrounding the tumor. This article (part 1) discusses the diagnostic and therapeutic specificities of these rare cancers, and develops the recommendations of the French ENT Cancer Expertise Network (REFCOR) concerning rare epithelial tumors, i.e., salivary tumors, sinonasal tumors, variants of conventional squamous cell carcinomas, neuroendocrine carcinomas, malignant odontogenic tumors, and ear tumors. A second article (part 2) is focused on non-epithelial tumors (sarcomas, mucosal melanomas, lymphomas, tumors of uncertain or undetermined malignancy) and describes the organization and missions of the REFCOR.

Exploring the Aggressiveness of Sarcomatoid Carcinoma of the Oral Cavity - an Institutional Experience.

Background: Sarcomatoid variant of squamous cell carcinoma in the oral cavity is a rare biphasic variant of squamous cell carcinoma. This aggressive variant of squamous cell carcinoma is characterized by invasive growth with marked local recurrence and distant metastasis resulting in poor prognosis. Sarcomatoid carcinoma can occur over a wide age range, incidence increases with older age and is a male-predominant disease. Methods: 23 patients with histologically proven Sarcomatoid SCC or with a sarcomatoid component (Group A) were compared with 23 randomly chosen patients with clinical stage IV (Group B) disease at the time of diagnosis, within the same time period and comparison was made between disease free survival and overall survival. Results: In group A, the mean DFS was found to be 12.4 months raging from 1 month to 36 months. 6 patients were therafter lost to follow follow up, in 11 patients the mean overall survival was found to be 8.72 months (ranging from 2 to 18 months) whereas 6 patients are alive till date. In group B, the mean DFS was found to be 19.56 months ranging from 6 months to 33 months. 4 patients succumbed to the disease with a mean overall survival of 24.25 years (ranging from 18 to 33 months), 4 patients were lost to follow up and the rest are alive till date. Conclusion: Sarcomatoid carcinoma of the oral cavity is an extremely rare but aggressive variant of conventional squamous cell carcinoma. We have to systematically understand their clinical, morphological and immunohistochemical features which is critical for their accurate diagnosis which aids in correct patient management. After radical surgery and adjuvant radiation therapy, strict follow up for development of recurrence and distant metastasis should be done.

Oral verrucous carcinoma: a diagnostic and therapeutic challenge.

Verrucous carcinoma is a low-grade variant of squamous cell carcinoma with specific morphologic, cytokinetic and clinical features. Despite low mitotic activity and slow growth, it can infiltrate adjacent tissues in advanced stages but does not metastasize. The most frequently affected site is the oral cavity. The following article provides latest updates in the etiology, clinical presentation, diagnostics and treatment options in oral verrucous carcinoma and discusses the existing dilemmas linked to this unique malignancy. Oral verrucous carcinoma must be differentiated from conventional squamous cell carcinoma due to its less aggressive behaviour with a more favourable prognosis. Close communication between clinician and pathologist is mandatory for making a correct diagnosis. Primary surgery with negative surgical margins seems to be the most successful treatment. However, management recommendations are not uniform since they are mostly based on case reports and small retrospective case series. Prospective and pooled multi-institutional studies are therefore needed.

Tumor-Stroma Ratio in Basaloid and Conventional Laryngeal Squamous Cell Carcinoma: Prognostic Significance and Concordance in Paired Biopsies and Surgical Samples

Basaloid squamous cell carcinoma (BSCC) is a subtype of squamous cell carcinoma (SCC) associated with a poor prognosis. Tumor-stroma ratio (TSR) has been introduced as a prognostic feature in many solid tumors. TSR was investigated in a series of laryngeal BSCCs and compared with a group of stage-matched conventional SCCs (cSCCs), in both preoperative and surgical specimens, with the intent of ascertaining the more aggressive behavior of BSCC and verifying the presence of stromal-related causes. A series of 14 consecutive laryngeal BSCCs and a control group of 28 stage-matched conventional cSCCs were analyzed. A higher nodal metastasis presence was found in BSCCs (57.1% vs. 28.6%). The recurrence rate was 33.5% and 63.6% in the cSCC and BSCC groups; disease-free survival (DFS) was higher, though not significantly, in patients with cSCC. TSR, large cell nests, and tumor budding showed a moderate to very good agreement, and stroma type a good to very good agreement between biopsies and surgical specimens in the cSCC group. In the BSCC group, agreement was poor to very good for TSR and stroma type, and good to very good for large cell nests and tumor budding. Age was the only feature significant in predicting recurrence in the BSCC group (p = 0.0235). In cSCC, TSR low/stroma rich cases, when evaluated on biopsies or surgical specimens, were associated with lower DFS (p = 0.0036; p = 0.0041, respectively). Laryngeal BSCCs showed a lower DFS than cSCCs, even if statistical significance was not reached. TSR, evaluated in laryngeal biopsies and excised tumors, was prognostic in terms of DFS in cSCC but not in BSCC cases.

Gross, Histologic and Immunohistochemical Characteristics of Keratoacanthomas in Lizards.

The present study describes the clinical behavior as well as the histopathologic and immunohistochemical characteristics of keratoacanthomas (Kas) in three different saurian species. While Kas presented as two dermal lesions in a bearded dragon (Pogona vitticeps), multicentric Kas were observed in three panther chameleons (Furcifer pardalis) and a veiled chameleon (Chamaeleo calyptratus). Macroscopically, Kas presented as dome-shaped skin tumors with a centralized keratinous pearl and a diameter ranging from 0.1-1.5 cm. In all lizards, Kas were predominantly located at the dorsolateral body wall, and KA of the eyelid was additionally observed in three out of four chameleons. Histologically, KAs presented as relatively well-defined, circumscribed epidermal proliferations that consisted of a crateriform lesion containing a central keratinous pearl with minimally infiltrating borders. In all KAs, a consistent immunohistochemical pattern was observed, with the expression of cyclooxygenase-2, E-cadherin, and pan-cytokeratin. A follow-up period of one to two years was established in all lizards. While no recurrence was observed in the panther chameleons, recurrence of a single keratoacanthoma was observed in the bearded dragon after one year, and in the veiled chameleon, multicentric keratoacanthomas reappeared during a follow-up period of two years. We describe KA as a previously unrecognized neoplastic entity in lizards that constitutes a low-grade, non-invasive but rapidly growing skin tumor that may show a multicentric appearance, especially in chameleons. As previously postulated for dermal squamous cell carcinomas (SCC), artificial ultraviolet lighting may play an important role in the oncogenesis of KAs in lizards. Although dermal SCCs in lizards show similar predilection sites and gross pathologic features, our results suggest that KA should be considered as a histologic variant of SCC that represents a rather benign squamous proliferation in comparison to conventional SCCs. Early diagnosis of KA and reliable discrimination from SCCs are essential for the prognosis of this neoplastic entity in lizards.

Early-stage glottic cancer of rare squamous cell carcinoma variants: a population-based study

Background Squamous cell carcinoma (SCC) is the most common histological type of laryngeal cancer. Several variants of SCC have been reported. However, how these variants differ from conventional SCC and how they should be treated remain to be elucidated. Objective To compare the prognosis of early-stage glottic cancer among SCC variants Methods We obtained data from 12471 cases using the Surveillance, Epidemiology, and End Results database. Disease-specific survival (DSS) and overall survival (OS) rates were estimated using the Kaplan–Meier method. A Cox proportional hazard model was used to estimate hazard ratios (HRs) according to the variants. Results HRs for DSS and OS compared with well-differentiated SCC were 3.83 and 3.48 for adenosquamous, 1.42 and 1.42 for basaloid, 1.14 and 1.17 for papillary, 0.85 and 0.94 for spindle, and 0.81 and 1.00 for verrucous SCC. The difference in DSS among the treatment modalities was significant in conventional and papillary SCC (p < .001 and p = .032, respectively). Conclusions The prognosis of SCC variants, except for adenosquamous SCC, is comparable to that of conventional SCC.

Evaluation of EGFR in prognostic characterization in histopathological variants of oral squamous cell carcinoma.

Epidermal growth factor receptor (EGFR) is a tyrosine kinase receptor of the Erb B family contributing to proliferation, invasion, and metastasis. EGFR overexpression is frequently associated with poor clinical outcome in malignant neoplasms.• To evaluate and compare immunoexpression of EGFR in histopathological variants of oral squamous cell carcinoma (OSCC).• To hypothesize the role of EGFR in determining biological behavior and prognostic course of histopathological variants of OSCC. The study comprised a total of 40 cases including 10 cases each of Squamous cell carcinoma, Verrucous carcinoma, Adenosquamous cell carcinoma, and Adenoid squamous cell carcinoma. EGFR immunoexpression was observed qualitatively as low (1), moderate (2) and strong (3) and quantitatively as score 1 for <10%, 2 for 10%-50%, and 3 for >50% positive cells. The resulting data were analyzed using SPSS software version 19. Data have been expressed as mean and standard deviation. Differences between the different variables were analyzed using ANOVA, and Pearson's Chi-square. (p ≤ 0.05). The study results revealed that the EFGR immunoexpression was highest in adenosquamous cell carcinoma followed by adenoid squamous cell carcinoma then conventional squamous cell carcinoma followed by lowest immunoexpression in verrucous carcinoma. The results were statistically significant. (p ≤ 0.05). Expression of EGFR could be established as a valuable biomarker with significant association in predicting aggressive potential and treatment response in various histopathological variants of OSCC. Further studies where EGFR could be linked to predictive indicators and tumor prognosis could be undertaken.

A comparative analysis of clinicopathological factors and survival between esophageal basaloid squamous cell carcinoma and conventional esophageal squamous cell carcinoma

IntroductionRecently, the number of diagnosed esophageal basaloid squamous cell carcinoma (EBSCC) has gradually increased. However, available data on EBSCC are limited to date. MethodsA total of 165 EBSCC (Cohort 1) and 515 conventional esophageal squamous cell carcinoma (ESCC) (Cohort 2) were retrospectively analyzed. ResultsIn Cohort 1, 70 cases only had invasive EBSCC component (42.4%, defined as Group 1), 73 cases had concomitant invasive ESCC component (44.2%, Group 2), and 22 had concomitant invasive poor-differentiated component (13.3%, Group 3). Lymph node metastasis rates of Group 3, Group 2 and Group 1 were ranked from high to low (P = 0.044). There were higher patient age (P = 0.047), smaller tumor size (P = 0.009), more nerve invasion (P < 0.001), and lower pTNM stage (P < 0.001) in EBSCC (Cohort 1), compared with ESCC (Cohort 2). In Cohort 1 and Cohort 2, pTNM stage was an independent prognostic factor for both DFS and OS. No significant survival difference was found between EBSCC (Cohort 1) and ESCC (Cohort 2) in pIA-B stage, pIIA-B stage, pIIIA-B stage and pIVA-B stage (P > 0.05). ConclusionOur analysis of the largest EBSCC series from a single institution to date with conventional ESCC demonstrated that EBSCC carried a similar prognosis with ESCC in pIA-B stage, pIIA-B stage, pIIIA-B stage and pIVA-B stage. And pure EBSCC, didn't have poorer survival than mixed EBSCC with concomitant ESCC or other components. Our findings may be valuable in the better understanding of EBSCC's biological behaviors, and the related molecular mechanism is needed to be explored in the future.

RB1-deficient squamous cell carcinoma: the proposed source of combined Merkel cell carcinoma

Merkel cell carcinoma (MCC) is an aggressive cutaneous neuroendocrine (NE) carcinoma arising from integration of Merkel cell polyomavirus (MCPyV) DNA into a host cell or from ultraviolet light-induced genetic damage (proportions vary geographically). Tumors in the latter group include those with “pure” NE phenotype and those “combined” with other elements, most often squamous cell carcinoma (SCC). We performed comprehensive genomic profiling (CGP) of MCPyV+ and MCPyV− (pure and combined) tumors, to better understand their mutational profiles and shed light on their pathogenesis. Supplemental immunohistochemistry for Rb expression was also undertaken. After eliminating low quality samples, 37 tumors were successfully analyzed (14 MCPyV+, 8 pure MCPyV− and 15 combined MCPyV−). The SCC and NE components were sequenced separately in 5 combined tumors. Tumor mutational burden was lower in MCPyV+ tumors (mean 1.66 vs. 29.9/Mb, P < 0.0001). MCPyV− tumors featured frequent mutations in TP53 (95.6%), RB1 (87%), and NOTCH family genes (95.6%). No recurrently mutated genes were identified in MCPyV+ tumors. Mutational overlap in the NE and SCC components of combined tumors was substantial (‘similarity index' >24% in 4/5 cases). Loss of Rb expression correlated with RB1 mutational (P < 0.0001) and MCPyV− status (P < 0.0001) in MCCs and it was observed more frequently in the SCC component of combined MCC than in a control group of conventional cutaneous SCC (P = 0.0002). Our results (i) support existing evidence that MCPyV+ and MCPyV− MCCs are pathogenetically distinct entities (ii) concur with earlier studies linking the NE and SCC components of combined MCCs via shared genetic profiles and (iii) lend credence to the proposal that an Rb-deficient subset of SCC's is the source of phenotypically divergent combined MCCs.