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2009 Mar 15;69(6):2568-76. Aggressive surgery with neck dissection yields an approximately 55% 2-year survival rate (Barnes et al., 2005; Thompson, 2006). Use of HPV vaccines against infection and therapeutic vaccines in the adjuvant setting for locoregional recurrence and distant disease should be assessed in this form of HNSCC. Most sinonasal LECs are associated with Epstein-Barr virus (EBV) infection (Barnes et al., 2005). Lassen P, Eriksen JG, Hamilton-Dutoit S, Tramm T, Alsner J, Overgaard J. J Clin Oncol. SCC is the most frequent malignant tumor of the head and neck region. These pathways are related to cellular proliferation, apoptosis, invasion, angiogenesis, and metastasis. However, overexpression of EGFR may be a biomarker for an improved response to therapy and could serve as a predictive marker (Bentzen et al., 2005). Znaor A, Brennan P, Gajalakshmi V, Mathew A, Shanta V, Varghese C, Boffetta P. Nat Rev Cancer. The tumor cells are plump fusiform cells, although they can be rounded and epithelioid. The tumor stains positive for vimentin and epithelial membrane antigen on immunohistochemistry. Overall 5 year disease free survival by tumor stage: Better prognosis for lymphoepithelial and verrucous variants, Worse prognosis with lower CD4+ cell counts in HIV seropositive patients (, 29 year old woman with cervical verrucous carcinoma (, 37 year old woman with cervical squamous cell carcinoma combined with adenoid basal carcinoma (, 47 year old pregnant woman with radical hysterectomy for cervical cancer (, 52 year old woman with cervical squamous cell carcinoma metastatic to the cerebellum presenting with pulmonary aspiration (, 55 year old woman with breast and splenic metastases of squamous cell carcinoma from the uterine cervix (, 64 year old woman with cervical squamous cell carcinoma metastatic to the orbital cavity (, Treatment follows the International Federation of Obstetrics and Gynecology (FIGO) and the National Comprehensive Cancer Network (NCCN) guidelines for cervical cancer according to stage (, Conization or loop electrosurgical excision procedure for low stage (IA) tumors (, Radical trachelectomy or radical hysterectomy with sentinel lymph node mapping or pelvic lymph node dissection with or without radiotherapy for higher stage tumors (, Radiotherapy and platinum based chemotherapy or pelvic exenteration for advanced tumors (, Red, friable, indurated or ulcerated lesion or elevated granular area in early stage tumors, Exophytic, papillary, polypoid, nodular or ulcerated mass, Deeply invasive mass with infiltration into surrounding structures, Tumor cells infiltrating as irregular anastomosing nests or single cells within desmoplastic or inflammatory stroma, Stromal loosening, desmoplasia or increased epithelial cell cytoplasmic eosinophilia in tumors with superficial stromal invasion, Grading is based on nuclear pleomorphism, size of nucleoli, mitotic activity and necrosis and does not correlate with prognosis, Well differentiated: variably shaped and sized nests with abundant keratin pearls, large cells with abundant eosinophilic cytoplasm and well developed intercellular bridges, occasional mitoses, necrosis may be present, Moderately differentiated: round to irregular and variably sized nests, cords and sheets, focal keratinization, large to medium sized and relatively uniform cells with indistinct cell borders, readily identifiable mitoses, Poorly differentiated: small nests, cords and sheets and single cells, small cells with scant cytoplasm, hyperchromatic nuclei and brisk mitoses, absent or rare keratinization, Keratin pearls, abundant keratohyaline granules and intercellular bridges, Large, hyperchromatic nuclei with coarse chromatin and inconspicuous nucleoli, Intercellular bridges but not keratin pearls, Large nuclei with unevenly distributed, coarsely granular chromatin and one or multiple nucleoli, Thin or broad papillae with fibrovascular cores lined by multilayered epithelium with squamous differentiation resembling HSIL, Stromal invasion may not be seen in superficial biopsies, Well defined nests of immature basaloid cells (resembling the cells of HSIL) with peripheral palisading of pleomorphic, hyperchromatic nuclei, brisk mitoses and scant cytoplasm, Focal keratinization but no keratin pearls, Resembles basaloid squamous cell carcinomas at other sites usually exhibiting an aggressive behavior, Warty surface and low power architecture resembling a condyloma or bowenoid lesion of the vulva, Keratinization and koilocytic atypia may be seen, Very rare and poorly understood form of squamous cell carcinoma in the cervix, Exophytic growth with undulating, warty surface and hyper or parakeratotic and frond-like acanthotic squamous epithelium, Broad based pushing invasion with bulbous epithelial pegs, Abundant cytoplasm, minimal cytologic atypia and rare mitoses, Resembles squamotransitional carcinoma of the urinary bladder, Papillae with fibrovascular cores lined by multilayered epithelium with transitional differentiation resembling HSIL, May occur in a pure form or in association with squamous elements, Not related to transitional cell metaplasia, Resembles nasopharyngeal lymphoepithelial-like carcinoma, Poorly defined nests of undifferentiated, discohesive squamous cells with uniform, vesicular nuclei, conspicuous nucleoli and moderate amounts of cytoplasm in a background of abundant lymphocytes, Indistinct cell borders impart a syncytial-like appearance, No evidence of keratinization and lack of intercellular bridges, Associated with HPV, not Epstein-Barr virus (EBV), Spindled cells with hyperchromatic nuclei, conspicuous nucleoli and brisk mitoses, May be admixed with more conventional epithelioid areas, Rare findings are focal mucinous differentiation, pseudoglandular pattern due to acantholysis, amyloid, signet ring cells, melanin granules, HSIL-like growth pattern (, Adequacy criteria: adequate if abnormal cells are seen irrespective of cellularity, Cellular specimens, usually with background tumor diathesis (fresh or hemolyzed blood and necrotic cellular debris), Tumor diathesis may not be seen in tumors with less than 5 mm depth of invasion or exophytic tumors (, Necrotic material at the periphery of cell groups (clinging diathesis) rather than in the background in liquid based preparations (, Large to medium sized nonkeratinized cells with high nuclear cytoplasmic ratio, Round nuclei with irregular contours, coarse, irregularly distributed chromatin and macronucleoli, Scant, dense basophilic cytoplasm without keratinization, Rare keratinized single cells may be seen, Dispersed cells and less prominent background diathesis, Markedly hyperchromatic nuclei with granular irregular chromatin and rare nucleoli, Irregularly shaped keratinized cells with orangeophilic cytoplasm, often with squamous pearls, Tadpole shaped cells with Herxheimer spirals and keratohyaline granules in cytoplasm, Compared to adenocarcinoma, cells and nuclei are more irregular with denser cytoplasm, greater chromatin granularity and nuclear hyperchromasia, Well developed intracytoplasmic tonofilaments, desmosome tonofilament complexes and intercellular microvilli in well differentiated tumors, lost with decreasing differentiation, Loss of heterozygosity (LOH) in multiple loci (1q, 3p, 3q, 6p, 6q, 11q, 17p, 18q) (. Pelucchi C, Talamini R, Levi F, Bosetti C, La Vecchia C, Negri E, Parpinel M, Franceschi S. Poeta ML, Manola J, Goldwasser MA, Forastiere A, Benoit N, Califano JA, Ridge JA, Goodwin J, Kenady D, Saunders J, Westra W, Sidransky D, Koch WM. Histogenesis SCC originates from the squamous mucosa or from ciliated respiratory epithelium that has undergone squamous metaplasia (Barnes et al., 2005). Recently, the use of targeted drugs has entered the field. The larynx is the most frequent site of occurrence. Once phosphorylated, it can signal through MAPK, Akt, ERK, and Jak/STAT pathways. Bonner JA, Harari PM, Giralt J, Azarnia N, Shin DM, Cohen RB, Jones CU, Sur R, Raben D, Jassem J, Ove R, Kies MS, Baselga J, Youssoufian H, Amellal N, Rowinsky EK, Ang KK. No special etiologic factor has been discovered for the mucosal acantholytic SCC. For comments and suggestions or contributions, please contact us, http://AtlasGeneticsOncology.org/Tumors/HeadNeckSCCID5078.html, Topo ( C30,C31,C03,C4,C04,C5,C05,C6,C06,C12,C13,C32,C00,C11,C69,C09,C10,C14,C07,C8,C08,C01,C2,C02,C33) arrayMap ((UZH-SIB Zurich), cBioPortal: Head and Neck Squamous Cell Carcinoma (Broad, Science 2011), cBioPortal: Head and Neck Squamous Cell Carcinoma (Johns Hopkins, Science 2011), cBioPortal: Head and Neck Squamous Cell Carcinoma (TCGA, Provisional), cBioPortal: Head and Neck Squamous Cell Carcinoma (TCGA, in revision), Head and Neck squamous cell carcinoma (HNSC) TCGA Copy Number Portal, Head and neck squamous cell carcinoma ( intOGen ), Head and Neck Carcinoma (TCGA)(OASIS Portal), Head and Neck Cancer Overview - Disease Synopsis [canSAR], Head and Neck Squamous Cell Carcinoma [ Genomic Data Commons - NCI TCGA-HNSC], Head and Neck: Squamous cell carcinoma: an overview, C301,C310-C313,C318-C319,C030-C031,C039-C041,C048-C052,C058-C062,C068-C069,C129-C132,C138-C139,C320-C323,C328-C329,C000-C006,C008-C009,C300,C110-C113,C118-C119,C690-C691,C693,C695-C698,C090-C091,C098-C104,C108-C109,C140,C142,C148,C079-C081,C088-C089,C019-C024,C028-C029,C339 ACCESSORY, SINUSES, MIDDLE & INNER EAR / GUM, FLOOR OF MOUTH, & OTHER MOUTH / HYPOPHARYNX / LARYNX / LIP / NASAL CAVITY (INCLUDING NASAL CARTILAGE) / NASOPHARYNX / ORBIT & LACRIMAL GLAND, (EXCL. HNSCC represents the sixth leading cancer by incidence and there are 500000 new cases a year worldwide (Kamangar et al., 2006). The tumor grows in a solid pattern with a lobular configuration, and sometimes a prominent peripheral palisading. 2010 Jul 1;363(1):24-35. Squamous carcinoma or squamous cell carcinoma is the name of a type of non-small cell lung cancer where the cells resemble the flat cells ... (such as immunohistochemistry), ... Poorly-differentiated carcinomas look very different from the cells from which they arose. Carcinoma in situ can be obscured by extensive ulceration. The larynx is the second most common site of VC in the head and neck region after the oral cavity. Epub 2010 May 5. However, locoregional recurrence develops in 30% to 40% of patients and distant metastases occur in 20% to 30% of HNSCCs (Forastiere et al., 2003). Nat Rev Cancer. What is the most likely diagnosis? The pseudolumina usually contain acantholytic and dyskeratotic cells, or cellular debris, but they may be empty. Extension into the underlying tissue is often accompanied by a desmoplastic stromal reaction and a dense inflammatory infiltrate, mainly comprised of lymphocytes and plasma cells. However, some reports suggest a more aggressive behavior (Barnes et al., 2005; Thompson, 2006). Both mutations and gene amplifications of MET have been described in HNSCCs. Most tumors are due to progression of a precursor lesion, Progression of HSIL is variable among women and may take decades, High risk HPV acts via E6 and E7 oncogenes (, E6 binds to tumor suppressor p53, causing its proteolytic degradation and inactivating p53 mediated DNA damage and apoptosis pathway, E7 binds to retinoblastoma gene (Rb), displacing transcription factors normally bound by Rb and inactivating Rb mediated cell cycle regulation pathway, Rb inactivation leads to overexpression of p16, a tumor suppressor gene involved in cell cycle regulation by inhibiting cyclin dependent kinases, p16 immunohistochemistry is used as a surrogate marker for high risk HPV infection, Usually spreads through cervical lymphatics to regional lymph nodes or via direct extension to vagina, uterus, parametrium, lower urinary tract, uterosacral ligaments; distant metastases may involve aortic and mediastinal lymph nodes, lungs, bones and adnexa, HPV vaccination of women 16 - 23 years of age offers durable protection for at least 12 years; the US Center for Disease Control (CDC) recommends HPV vaccination in 2 or 3 doses depending on age (, Two doses for children and adolescents of any gender ages 9 - 14 years, Three doses for adolescents and adults of any gender ages 15 - 26 years, Nearly all cases are associated with persistent infection by high risk HPV subtypes such as 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68 and others (, HPV 16 is the major causal agent for squamous cell carcinoma, in contrast to HPV 18 typically associated with endocervical adenocarcinoma, Younger age at first intercourse and higher lifetime number of sexual partners (, Single contact with infected partner may result in infection and risk plateaus with many contacts (, Immunodeficiency, including human immunodeficiency virus (HIV) infection, transplantation and medications (, Multiparity and early age at first birth (, Chronic inflammation or concurrent sexually transmitted diseases, such as chlamydia, Abnormal cervical cytology in asymptomatic patients, Pain, urinary symptoms (ureteral obstruction leading to anuria or uremia, hematuria, frequency, vesicovaginal fistula), gastrointestinal symptoms (tenesmus, rectovaginal fistula), lymphedema in the lower extremities in advanced tumors, Histologic examination of biopsy or excisional material, Only tumors that are at least stage IB can be identified radiologically (, Magnetic resonance imaging (MRI) is the imaging modality of choice to assess the extent of primary tumor (, Mass lesion with a high signal relative to the low signal of the cervical stroma, Hypoechoic, heterogeneous mass, sometimes with increased vascularity on color Doppler, Adenopathy and metastatic disease is best assessed with computed tomography (CT), Positron emission tomography (PET) may also be used to rule out metastases (, Tumor stage, patient age, depth of invasion, disease volume, lymphovascular invasion (. High-risk oncogenic HPV subtypes have been shown to be capable of transforming oral epithelial cells through the viral oncoproteins E6 and E7. 1999 May 8;318(7193):1289-90; author reply 1291. The majority of laryngeal SCCs originate from the supraglottic and glottic regions. Small cystic spaces containing PAS- and Alcian Blue-positive material and stromal hyalinization may be noticed. Occasionally, patients harbor enlarged cervical lymph nodes with no identifiable oral or oropharyngeal lesion. It is poorly differentiated and cannot be further classified by immunohistochemistry (IHC) or electron microscopy. However, 10% of the patients are asymptomatic (Barnes et al., 2005; Thompson, 2006). Hypopharynx, larynx, and trachea Hypopharyngeal and supraglottic tumors may be responsible of dysphagia, change in quality of voice, foreign body sensation in the throat, haemoptysis, and odynophagia. Well-differentiated SCC closely resembles normal squamous mucosa whereas moderately-differentiated SCC displays nuclear pleomorphism, mitoses (including atypical forms), and usually less keratinization (Fig. J Clin Oncol. Epub 2009 Mar 10. 2008 Jul 1;26(19):3128-37. Cancer Res. (REVIEW). 2008 Mar 19;100(6):407-20. Nasal symptoms, particularly blood-stained post-nasal drip are reported in half the cases. CUSTOMER SERVICE: Change of address (except Japan): 14700 Citicorp Drive, Bldg. HPV-16 and -18) (zur Hausen, 2002; Moody et al., 2010). Spindle cell carcinoma Spindle cell carcinoma is a biphasic tumor composed of a squamous cell carcinoma, either in situ and/or invasive, and a malignant spindle cell component with a mesenchymal appearance, but of epithelial origin (Barnes et al., 2005). 0.5 percent of lung adenocarcinomas, and 3 percent of squamous cell carcinomas of the lung [5]. Though squamous papilloma and verrucous carcinoma share similar architectural features with PSCC, the latter is easily recognized by atypia of the squamous epithelium. The most common oropharyngeal site of involvement is the base of the tongue. The most important differential diagnosis is from mucoepidermoid carcinoma as adenosquamous carcinoma has a poorer prognosis. The differential diagnosis includes neuroendocrine carcinoma, adenoid cystic carcinoma, and adenosquamous carcinoma. Primary prevention could be achieved by cessation of smoking and reduction of alcohol consumption. Marur S, D'Souza G, Westra WH, Forastiere AA. The surface is frequently ulcerated. HPV infection is an early, and probably initiating, oncogenic event in HNSCCs. Clinical features vary according to the exact site of the lesion. In poorly-differentiated lesions, immunohistochemistry may be useful. The junction between the two components may be abrupt. 2003 Jan;129(1):106-12. 4-6). Histopathologically, the tumor is often moderately to poorly-differentiated with basaloid features (Gillison et al., 2000). Elevated levels of EGFR expression have been associated to a poor clinical outcome (Chung et al., 2004; Temam et al., 2007). J Clin Pathol. The E6 protein induces degradation of p53 through ubiquitin-mediated proteolysis, leading to substantial loss of p53 activity. Epub 2009 Mar 16. The SCC component predominates, and is usually moderately-differentiated. 2007 Dec 20;357(25):2552-61. There also seems to be an inverse relationship between EGFR expression and HPV status. ... Squamous Cell Carcinoma of the Vulva (CUK, Exp Mol Med 2018) 15 samples. They are more frequent in the deeper portions of the tumor. The tumor is characterized by a predominant papillary growth pattern. Nasal and paranasal sinuses Patients with SCC arising in the nasal or paranasal sinuses may complain of nasal fullness, stuffiness, or obstruction, but also of epistaxis, rhinorrhea, pain, paraesthesia, swelling of the nose and cheek or of a palatal bulge. However, HPV-positive HNSCCs are associated with a more favorable clinical outcome regardless of treatment modalities, and this may be related to immune surveillance to viral antigens (Leemans et al., 2011). Binding of the antibody to EGFR prevents activation of the receptor by endogenous ligands. P16 immunohistochemistry could serve as a potential surrogate marker (Marur et al., 2010). 2006 Sep 1;12(17):5064-73. NUT carcinoma is an undifferentiated or poorly differentiated squamous cell carcinoma, meaning the cancer begins in squamous cells in the body. The papillary pattern consists of multiple, thin, delicate, finger-like papillary projections. 2006. In contrast, Fibroblast growth factor receptor 1 is mainly amplified with only rare translocation events reported in glioblastomas, breast cancer and lung squamous cell carcinomas [5]. Evidence for squamous epithelial derivation can be seen as either in situ carcinoma or as invasive SCC. It is an aggressive, rapidly growing tumor characterized by an advanced stage at the time of diagnosis (cervical lymph node metastases) and a poor prognosis. Infiltrating SCC may be focal, requiring multiple sections for demonstration. Lewis JS Jr, Thorstad WL, Chernock RD, Haughey BH, Yip JH, Zhang Q, El-Mofty SK. It frequently arises from a thin stalk, but broad-based lesions have also been described. This is the one SCC variant in which immunohistochemistry may be of value.

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