Variant Of Squamous Cell Carcinoma Research Articles

Esophageal carcinoma cuniculatum: a narrative review to understand this rare and commonly misdiagnosed variant of well-differentiated esophageal squamous cell carcinoma.

Esophageal carcinoma cuniculatum (CC) is a rare variant of a well-differentiated squamous cell carcinoma (SCC). Unlike other forms of esophageal cancers, CC of the esophagus is difficult to diagnose on endoscopic biopsies. This can lead to a delay in the diagnosis and increases morbidity. We reviewed the available literature to shed light on the etiopathogenesis, diagnosis, treatment, and outcomes of this disease. Our aim is to create a better understanding of this rare disease entity and contribute to a timely diagnosis to reduce the associated morbidity and mortality. Extensive review of PubMed, Embase, Scopus, Google Scholar was conducted. We identified the published literature on Esophageal CC from inception till date. We report epidemiological trends, clinical presentation, diagnostic and treatment strategies to correctly identify the cases to reduce the likelihood of a missed diagnosis of esophageal CC. Associated risk factors for esophageal CC are chronic reflux esophagitis, smoking, alcohol consumption, immunosuppression, and achalasia. Dysphagia is the most common presentation. Primary diagnostic modality is an esophagogastroduodenoscopy (EGD), but diagnosis can be easily missed. To favor an early diagnosis, a histological scoring system has been proposed by Chen et al. where authors describe specific histological features that appear to be common based on the numerous mucosal biopsies examined from patients with CC. A high clinical suspicion for the disease along with close endoscopic follow-up with repeat biopsies is needed for an early diagnosis. Surgery remains the gold standard for treatment and is associated with a favorable prognosis when the patients are diagnosed early.

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.

Distant metastasis in head and neck squamous cell carcinoma variants: A population-based study.

Head and neck squamous cell carcinoma (HNSCC) with distant metastasis (DM) has poor prognosis. HNSCC has several histological variants with varying characteristics. We investigated the DM rates and prognoses of patients with DM among the HNSCC variants. We obtained data from 54 722 cases using the Surveillance, Epidemiology, and End Results database. Odds ratios (ORs) for DM and hazard ratios (HRs) for overall survival (OS) were estimated using a logistic regression model and a Cox proportional hazard model, respectively. DM rate was the lowest in verrucous carcinoma and the highest in basaloid squamous cell carcinoma (BSCC) (0.2% and 9.4%, respectively). ORs for DM were 3.63 for adenosquamous carcinoma, 6.80 for BSCC, and 3.91 for spindle cell carcinoma (SpCC). SpCC was significantly associated with a poor OS (HR, 1.61). DM rates differed among the HNSCC variants. The prognosis of metastatic SpCC is worse than that of other metastatic HNSCCs.

The Versicolour Gyre-Squamous Cell Carcinoma-Anal Canal: A Mini Review

Squamous Cell Carcinoma (SCC) of anal canal is a frequently discerned malignant neoplasm confined to the anal tract. Thus denominated by World Health Organization (WHO), the neoplasm exemplifies primary squamous cell carcinoma of anus. Basaloid variant of squamous cell carcinoma is additionally designated as cloacogenic or transitional cell carcinoma of anal canal. Besides, mucoepidermoid carcinoma of anal canal denominates neoplasms delineating prominent features of mucinous transition.

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.

Solid Variant of Adenoid Cystic Carcinoma Coexisting with Invasive Squamous Cell Carcinoma in Uterine Cervix – A Case Report with Immunoprofile

Primary adenoid cystic carcinoma of cervix is a rare entity. Co-existence of adenoid cystic carcinoma with squamous cell carcinoma is even more rare. Here we present the case of an 85 year old postmenopausal lady who presented with on and off vaginal bleeding and was found to have a hard cervical mass. Hysterectomy with bilateral salpingo-oophorectomy was done and histopathological evaluation revealed coexisting solid variant of adenoid cystic carcinoma and squamous cell carcinoma. High grade squamous intraepithelial lesion was seen adjacent to invasive squamous cell carcinoma. Adenoid cystic carcinoma was positive for CD117 and squamous cell carcinoma was positive for p63. Both the components were also immunoreactive for p16.

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.

Spindle Cell Carcinoma Arising in Xeroderma Pigmentosum-A Rare Tumour in a Rare Disease.

Dear Editor, Xeroderma pigmentosum (XP) is recognized by cutaneous photosensitivity to ultraviolet radiation leading to pigmentary changes, photophobia, and tendency to develop malignancies such as squamous cell carcinoma (SCC), basal cell carcinoma (BCC), and melanoma.[12] Spindle Cell Carcinoma (SpCC) is an extremely rare variant of SCC. A case of extremely rare spindle cell squamous cell carcinoma (SpSCC) developing in the setting of XP on the cheek of a 9-year-old boy is presented here. A 9-year-old boy, known case of XP, presented to the hospital with an erythematous nodule on the cheek [Figure 1] of size 3 × 3 cm. The patient also had multiple brown to black lentigines of size 0.1 × 0.1 cm intermixed with hypopigmented macules of size 0.1 × 0.1 cm to 0.4 × 0.4 cm over photo exposed areas of the face, neck, chest, upper back, bilateral upper and lower limbs, palms, and soles. A provisional diagnosis of BCC was rendered, nodule excised, and sent for histopathological examination. Microscopic sections revealed a biphasic tumor composed of atypical squamous cells with the presence of squamous pearls in the superficial part of the biopsy [Figure 2]. The deeper part of the lesion exhibited spindle cells in fascicles with greater atypia and the presence of atypical mitosis (2–3/10 high power fields) [Figure 3]. The transition from the squamous cell to spindled cell was quite prominent [Figure 4]. No necrosis was noted. On immunohistochemistry (IHC), there was co-expression of cytokeratin (CK) [Figure 5a] and vimentin [Figure 5b]. The tumor cells were negative for S100 and HMB45. A histopathological diagnosis of SpCC was rendered.Figure 1: Erythematous nodule over the right cheek near-eye with central black crustingFigure 2: Atypical squamous cells with the presence of squamous pearls. (H and E, ×400)Figure 3: Spindled areas with greater atypia. (H and E, ×400)Figure 4: Transition of atypical squamous cells into spindle cells (H and E, ×40)Figure 5: (a) Cytokeratin expression in squamoid areas (IHC, ×400). (b) Vimentin expression in spindled areas (IHC, ×400)The basic defect in XP is the deficient repair of DNA damaged by UV radiation making XP a model disease for sun-induced carcinogenesis. Damaged DNA is removed with the help of NER replaced by new DNA.[3-5] SpCC is a rare poorly differentiated variant of SCC, which portends a worse prognosis compared to the usual SCC. Seen mostly in men in the sixth and seventh decades, it accounts for 1% of all SCCs and mostly is found in the oral cavity, larynx, pharynx. and sinonasal locations. Primary SpSCC of the skin is extremely rare.[5] Exposure to ultraviolet radiation is one of the most important etiological factors in the development of SpSCC. It usually occurs in the backdrop of solar elastosis and lacks keratinization. Exposure to ultraviolet radiation coupled with DNA repair defects possibly made this patient extremely vulnerable to this aggressive neoplasm.[25] The histological diagnosis is quite challenging. The absence of basaloid cells, peripheral palisading, and retraction clefts excluded BCC. Keratoacanthoma was excluded as there was the absence of a keratin-filled central crater surrounded by the epidermal lip. The presence of invasion into the subcutis, absence of actinic changes, and presence of a connection to the overlying epidermis and positivity for CK ruled out atypical fibroxanthoma. Different theories have been proposed to explain the origin of SpCC. It could possibly arise as a result of dedifferentiation of the spindle cells to the epithelial component. The second theory supports the theory of collision tumors and lastly, some studies report that the spindle component may be a reactive proliferation of the stroma.[15] Thus, XP is a rare disease and SpSCC developing in its backdrop further makes it challenging to timely diagnose and manage the condition. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

Germline Pathogenic Variants in Squamous Cell Carcinoma of the Head and Neck.

Head and neck squamous cell carcinoma (HNSCC) presents a significant global health problem with variable geographic distribution and risk factors, including tobacco and alcohol abuse, human papillomavirus infections, and genetic predisposition. While the majority of cases are sporadic, several well-defined hereditary syndromes have been associated with a higher risk of developing HNSCC including Li-Fraumeni syndrome, Fanconi anaemia, Bloom syndrome, familial atypical multiple mole melanoma, and dyskeratosis congenita. There is also evidence of familial clusters of HNSCC, suggesting a genetic component in the development of the disease. Germ-line genetic testing in HNSCC using next-generation sequencing has revealed a wide range of germline variants, some of which were not anticipated based on standard guidelines. These variants may influence treatment decisions and have the potential to be targeted with precision medicine in the future. Despite these advances, routine germline genetic testing for HNSCC is not currently recommended and remains reserved for HNSCC cases with early onset or strong family cancer history. However, the increasing availability of germline genetic testing warrants development of more comprehensive and standardized testing protocols. Germline genetic testing also has the potential to influence precision-guided treatment in HNSCC patients carrying germline pathogenic variants.

Vulvar Sarcomatoid Squamous Cell Carcinoma: A Rare Entity

Vulvar squamous cell carcinoma with sarcomatoid features is an extremely rare histological variant of squamous cell carcinoma with co-existence of both epithelial and mesenchymal features. A 70-year-old woman presented with genital lesions for 4 months with associated burning and pain. Examination revealed well-defined bilaterally symmetrical hyperpigmented plaques on labia majora, fleshy erythematous growth on labia minora. Biopsy from the fleshy mass was suggestive of sarcomatoid malignancy. However, immunohistochemistry was positive for cytokeratin AE1/AE3 and negative for desmin and smooth muscle actin. Biopsy from hyperpigmented plaque was suggestive of Bowens disease. On the basis of histopathology and immunohistochemistry findings, diagnosis of vulvar sarcomatoid squamous cell carcinoma with Bowens disease was made and patient was started on external beam radiation therapy. Sarcomatoid squamous cell carcinoma of vulva is very rare cancer that has an aggressive and fatal course. Diagnosis has traditionally been difficult due to a large ratio of sarcomatous to squamous cell component. Due to its rarity, there are no distinct guidelines to direct therapy and care.

An Update on WHO Classification of Thoracic Tumours 2021- Newly Described Entities and Terminologies

The 5th edition of the World Health Organisation (WHO) “Classification of Thoracic Tumours” replaces the previous edition from 2015, which was released in 2021. The new edition includes specific diagnostic criteria for each entity and lays a stronger emphasis on diagnostic molecular pathology. Immunohistochemistry (IHC) was heavily promoted in 2015, as a way to improve classification precision. The book places more attention on molecular pathology developments for all tumour types in 2021. Classification based on microscopic biopsy samples of the characteristics of lung cancer is an alternative to resection-based categorisation. A grading system for invasive non mucinous adenocarcinomas has been developed, using the percentage of distinctive histological patterns found inside each tumour. Lung adenocarcinoma is also predisposed by Tumour Spread Through Air Spaces (STAS). A basaloid variety of Squamous Cell Carcinoma (SCC) and lymphoepithelial carcinoma was added to the SCC group. The ciliated muconodular papillary tumour and thoracic SMARCA4-deficient undifferentiated carcinoma are recent inclusions. Therefore, the following new terms and entities have been added to the WHO classification of 2021: (1) Thoracic SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 4 (SMARCA4)-deficient undifferentiated tumour; (2) Bronchiolar adenoma/ciliated muconodular papillary tumour; (3) Primary pulmonary hyalinising clear cell carcinoma of lung; (4) Lypmphoepithelial carcinoma; (5) STAS.

Mixed warty and sarcomatoid squamous cell carcinoma of vulva: a rare occurrence

Vulvar cancer is a rare tumor accounting for &lt;5% of female genital tract tumors. The most common type of vulvar malignancy is squamous cell carcinoma. There are many histological variants of squamous cell carcinoma, keratinizing type being the most common one. Sarcomatoid variant is an extremely rare variant in vulva and comprises both epithelial and mesenchymal features. Due to the rarity of this tumor in the vulva and limited cases reported in the literature, no proper management guidelines have been established yet. In the current case report, we describe a case of mixed warty and sarcomatoid squamous cell carcinoma of vulva.

CLEAR CELL VARIANT OF SQUAMOUS CELL CARCINOMA PENIS – A CASE REPORT

Carcinoma penis is a rare malignancy in males. The World Health Organization Classification of Tumors of the Urinary System and Male Genital Organs classifies squamous cell carcinoma of the penis into human papillomavirus (HPV) and non HPV related. Among the HPV-related Squamous cell carcinomas of the penis, clear cell variant is a rare. Here we report a case of clear cell variant of squamous cell carcinoma of penis with bilateral inguinal lymph node metastasis. We have treated this patient with radical surgery, wide excision and bilateral inguinal lymph node dissection followed by post operative chemo radiation. But during radiation itself the disease progressed, with rapid recurrence of inguinal lymph node metastasis, finally end up with palliative chemotherapy. Clear cell carcinoma is an aggressive form of cancer, with frequent metastasis to the inguinal lymph nodes, as seen in this case. Immunohistochemistry examination P16 was absent. So it is considered as clear cell variant of squamous cell carcinoma. Clinical experience with penile carcinoma is limited because of their rarity.

Histomorphological variants of oral squamous cell carcinoma and their relation with prognosis of the disease

The key to wealth is health but in present days cancer is going to exhaust mental, physical and economic conditions. Oral Cancer is the 6 most common cancer worldwide. Approximately 630,000 new patients diagnosed annually resulting in more than 350,000 deaths every year. Squamous cell carcinoma is by far the most important and the most common malignant mucosal neoplasm of the head and neck accounting for over 90% of all malignancies.Histomorphological features of oral squamous cell carcinoma (OSCC) and their relation with the pathological prognostic factors i.e. histological stage and grade of malignancy is the key feature, which help early and easy prognosis of OSCC. :To study the histomorphological features of oral squamous cell carcinoma and their relation with the pathological prognostic factors i.e. histological stage and grade of malignancy. Recent reports suggest an increase in oral squamous cell carcinoma (OSCC) frequency. To improve programs in public health, it is necessary to understand the epidemiological conditions. A retrospective review of all OSCC cases diagnosed by the Pathology Department was performed. Demographic data, in addition to anatomic zone and histological degree of differentiation were obtained. Central tendency, dispersion and prevalence rate per 100,000 individuals were determined. A total of 150 patients were diagnosed with OSCC and majority of them were men 118(79%) were men. OSCC were predominantly observed in the age of 40-60 years. The predominant anatomic zone was the Buccal mucosa, GBS, Angle of Mouth 99(66%), followed by the tongue and lip 42(28%) and Retromolar Triagone 09(06%).The most frequent histological degree was well differentiated in 110 cases (73.3%). The rates of OSCC prevalence showed similar patterns in terms across time.

BASALOID SQUAMOUS CELL CARCINOMA- A RARE METATYPICAL TUMOR- CASE REPORT

A rare kind of squamous cell cancer is called basaloid squamous cell carcinoma occurring in sixth to seventh decade of life with male predilection. It preferentially occurring in upper aerodigestive tract. Rare case reports are presented in the classical age group with a poor prognosis. A 46 year's senior old male patient showed up to otorhinolaryngology department with chief complain of growth on base on left side of tongue and supra-glottic growth. On radiological evaluation by Multislice CT Scanning, a heterogeneously enhancing mass lesion measuring approximately 25×38 mm was noted at the base of tongue. On cytological evaluation of the lesion, highly cellular smear showed malignant morphology of the cells. Histological evaluation reveals a tumour mass in which neoplastic cells were composed of two different cell types – the majority of the cells population consisted of basaloid cells with abrupt association of foci of squamous cells suggesting basaloid variant of Squamous cell carcinoma. We brought this case for acknowledgment due to its rare occurrence, lower age of presentation, poor prognostic value as well as high metastatic potential.

Mohs micrographic surgery in rare cutaneous tumors: a retrospective study at a Brazilian tertiary university hospital

BackgroundMohs micrographic surgery is an established technique in the treatment of cutaneous neoplasms. It offers higher cure rates and the main indications are non-melanoma malignant skin tumors. Few studies have been performed on the treatment of rare tumors through this technique. ObjectiveTo study rare skin tumors and rare variants of basal cell carcinoma and squamous cell carcinoma submitted to Mohs micrographic surgery in a tertiary service in relation to frequency, disease-free evolution, and applicability of this surgical procedure for this group of tumors. MethodsThis was a retrospective observational study including rare skin tumors and less common variants of basal cell carcinoma and squamous cell carcinoma treated using Mohs micrographic surgery, between October 2008 and April 2021. ResultsDuring the study period, 437 tumors were treated using Mohs micrographic surgery, and 22 (5%) rare skin tumors were selected. The tumors comprised three dermatofibrosarcomas protuberans, two atypical fibroxanthomas, two spiradenomas, two hypercellular fibrohistiocytomas, one primary cutaneous adenocarcinoma, one trichoblastoma, one porocarcinoma, one chondroid syringoma, one cutaneous angiosarcoma, one Merkel cell carcinoma, and one sebaceous carcinoma. Six other cases of rare basal cell carcinoma variants with trichoepitheliomatous differentiation, metatypical basal cell carcinoma, and clear cell squamous cell carcinoma were included. There were no cases of recurrence after an average of six years of follow-up. Study limitationsThis is a retrospective study on rare neoplasms carried out in a single referral center, and this surgical technique isn’t widely available in the public service. ConclusionThis retrospective case series showed that Mohs micrographic surgery is an appropriate treatment for rare skin tumors. They corresponded to 5% of the tumors treated by the technique during a 12-year-period, with no recurrences identified.

Radiation vs surgery for early-stage laryngeal verrucous carcinoma: A population-based propensity score matched-study.

Verrucous carcinoma (VC) is a rare variant of squamous cell carcinoma. Although VC is considered radioresistant, concrete evidence for this is absent. We obtained data on VC treated with surgery or radiation from the Surveillance, Epidemiology, and End Results database. Treatment selection bias was reduced by propensity score matching. Overall survival (OS) and disease-specific survival (DSS) rates were estimated using the Kaplan-Meier method. Hazard ratios (HRs) were estimated using Cox proportional hazards models. Five-year OS rates in the radiation and surgery groups were 72.7% and 72.0%, respectively (P = 0.111); five-year DSS rates in the same were 86.7% and 88.4%, respectively (P = 0.234). HRs of radiation compared with surgery were 1.68 (95% confidence interval (CI), 0.96-2.95) for OS and 1.95 (95% CI, 0.69-5.53) for DSS. Similar prognoses were observed in patients with VC treated with radiation and surgery. VC can be treated using radiation.

Spindle Cell Carcinoma of the Head and Neck: Clinical Characteristics and Molecular Signatures.

Spindle cell carcinoma of the head and neck (HNSpCC) is a rare variant of head and neck squamous cell carcinoma (HNSCC). This study evaluated the clinical characteristics and molecular signatures of such tumors. Retrospective analysis. Medical records of patients diagnosed with HNSpCC from 1996 to 2018 were reviewed. The clinicopathologic features, treatment modalities, and survival status were carefully recorded. Whole exome sequencing (WES) was performed to evaluate the genetic signatures of HNSpCC. We found that among all 71 patients included in this study, the majority of them were male, with tumors developing predominantly in the oral cavity. The 1-, 3-, and 5-year disease-specific survival (DSS) rates were 64.6%, 49.5%, and 43.9%, respectively. A high local recurrence (LR) and distant metastasis (DM) rate (47.9%-25.3%, respectively) were observed. A significant proportion (28.2%) of patients with the worst prognosis had history of previous head and neck cancer (HNC) and had been treated with radiotherapy (RT). WES revealed that those post-RT SpCC shared common mutations with their previous HNC (pre-RT SCC), but gained additional genetic traits, such as hypoxia and cell-ECM interaction that were favorable for survival in an irradiated microenvironment. Distinct genetic landscapes in primary and post-RT SpCC were also found. This study demonstrates that HNSpCC is a unique entity with more aggressive behavior than conventional HNSCC. HNSpCC arising from a previously irradiated field is a predictor of dismal survival. Both genetic and microenvironmental factors contribute to this highly invasive tumor. 4 Laryngoscope, 133:2183-2191, 2023.

Outcomes of Patients with Adenosquamous Carcinoma of the Head and Neck after Definitive Treatment

<h3>Purpose/Objective(s)</h3> Adenosquamous carcinoma of the head and neck (ASC-HN) is a rare and aggressive variant of squamous cell carcinoma (SCC). Limited data suggests inferior outcomes compared to conventional SCC. We report one of the largest single institutional experiences of this disease in patients treated definitively to further elucidate oncologic outcomes. <h3>Materials/Methods</h3> Patients with non-metastatic ASC-HN treated definitively between 2003 and 2021 were identified retrospectively from an IRB approved database with histology verified by head and neck pathologists. All tumors of the oropharynx were tested for p16 and/or HPV to document HPV associated disease. For non-oropharyngeal lesions, a designation of HPV positivity required the presence of HPV DNA/RNA per CISH. Actuarial analyses were performed for PFS and OS. <h3>Results</h3> 29 patients with ASC-HN (72.4% male, 93.1% Caucasian) with median age of 66 (range 34-91) and a median follow up of 33 months (range 6.6-126.7) were identified. The most common primary tumor sites were: oropharynx (27.6%), oral cavity (20.7%), nasal cavity (17.2%), and larynx (17.2%). 3 patients had primaries in the hypopharynx, nasopharynx and parotid gland respectively. 11 patients (37.9%) were HPV positive of whom 8 had oropharyngeal primaries. The majority (n=23, 79.3%) were treated with primary surgery of whom 19 (82.6%) received adjuvant radiation (RT) to a median dose of 60 Gy (range 36-70 Gy) with 7 receiving concurrent chemotherapy. 6 patients were treated with definitive RT to a median dose of 70 Gy with two receiving concurrent chemotherapy. There were 10 recurrences (34.5%) which occurred at a median of 14.3 months (range 5.4-28) after diagnosis including 8 loco-regional and 2 distant recurrences. Recurrences were documented in patients with primary salivary gland, oral cavity, laryngeal, hypo-pharyngeal, and oropharyngeal tumors. 3 of the 10 recurrences were in patients with HPV positive disease. Among the 6 patients treated with definitive radiation or chemo-radiation no failures were observed. 9 patients (31%) were deceased at the time of analysis. Overall, 3-year PFS and OS were 54.2% and 72.9%, respectively. 3-year PFS and OS were 45.6% and 69.6% for primary surgery and 83.3% and 83.3% in the definitive RT group. 3-year PFS was 50% and 75% for HPV negative and positive patients respectively. <h3>Conclusion</h3> In our single institutional experience of 29 patients with adenosquamous carcinoma of the head and neck there was a 34.5% recurrence rate. Loco-regional recurrence was the primary mode of failure.