Squamous cells normally line hollow organs in the body, such as the respiratory tract. (REVIEW), Nat Rev Cancer. Foci of necrosis and hemorrhage are common. Precursor lesions (dysplasia) can be (arbitrarily) separated into mild, moderate, or severe (carcinoma in situ) (see below). Aggressive surgery with neck dissection yields an approximately 55% 2-year survival rate (Barnes et al., 2005; Thompson, 2006). Well-differentiated SCC closely resembles normal squamous mucosa whereas moderately-differentiated SCC displays nuclear pleomorphism, mitoses (including atypical forms), and usually less keratinization (Fig. Cancer of soft palate and uvula often appears as an ulcerative lesion with raised margins or as a fungating mass. Mutations and amplifications of EGFR have been reported, albeit at relatively low frequencies. Increased survival of patients with HPV-positive SCC may be in part attributable to absence of dysplastic fields related to tobacco and alcohol exposure. However, only the rate of locoregional recurrence, but not that of distant disease, is diminished in patients with HPV-positive SCC. Lewis JS Jr, Thorstad WL, Chernock RD, Haughey BH, Yip JH, Zhang Q, El-Mofty SK. SCC is graded into well-, moderately-, and poorly-differentiated. Invasive carcinoma arises from squamous cell carcinoma in situ as part of the dysplasia-carcinoma sequence Especially in high risk areas, a lack of fruits and vegetables causing deficiencies of vitamins A, B6, C, riboflavin, thiamine, zinc and molybdenum are likely involved HNSCC represents the sixth leading cancer by incidence and there are 500000 new cases a year worldwide (Kamangar et al., 2006). Churchill Livingstone Elsevier, Philadelphia. Microscopically, the thickened, club-shaped, projections are lined by well-differentiated squamous epithelium devoid of the malignant features commonly seen in SCC. It is poorly differentiated and cannot be further classified by immunohistochemistry (IHC) or electron microscopy. Uterus with cervix, fallopian tubes and ovaries, radical hysterectomy and bilateral salpingo-oophorectomy: Cervix: invasive squamous cell carcinoma (see synoptic report), Well / moderately / poorly differentiated, Lymphovascular space invasion: present / absent (if present, extent), Margins (ectocervical / endocervical / vaginal / deep / parametrial / radial): positive or negative (if negative, distance to carcinoma in mm), Papillary, tubulocystic and solid growth patterns, hobnail cells, no squamous differentiation, Deeply infiltrative nests of basaloid squamous cells with nuclear palisading and focal lumina, no desmoplastic stromal reaction, Cribriform, solid and tubular growth patterns, luminal epithelial cells and basal cells, basement membrane-like material, Nests, cords, trabeculae and rosettes of small cells with scant cytoplasm, hyperchromatic nuclei with molding and crush artifact, brisk mitoses, apoptotic debris, geographic necrosis, Malignant mesenchymal component with or without heterologous elements, Well circumscribed tumor with neoplastic cells arranged around vessels and areas of necrosis, no keratinization, Uniform cells lacking significant nuclear atypia, Well circumscribed nodules of bland intermediate trophoblast cells, no keratinization, no or rare mitotic activity, Well defined nests with smooth borders, preserved polarity of basal epithelial cells, no abrupt maturation at interface, no desmoplastic stromal reaction, Negative p63, p40, CK5/6, p16; positive CK18, napsin A, inhibin, HPL, Positive CK5/6, p16, inhibin; negative p63, p40, CK18, napsin A, HPL, Positive CK18, p16, p63, inhibin, HPL; negative napsin A, p40, CK5/6, Positive p63, p40, CK5/6, p16; negative CK18, napsin A, inhibin, HPL, HPV 16, history of HSIL, multiple sexual partners, multiparity, smoking, immunodeficiency, HPV 16, history of HSIL, multiple sexual partners, nulliparity, smoking, immunodeficiency, HPV 16, history of LSIL, multiple sexual partners, nulliparity, smoking, immunodeficiency, HPV 18, history of LSIL, single sexual partner, multiparity, smoking, immunodeficiency, Most cervical squamous cell carcinomas are associated with HPV 18, Nearly all cases of cervical squamous cell carcinoma are associated with high risk HPV and arise from a precursor lesion, HSIL, Poorly differentiated squamous cell carcinomas are associated with high risk HPV subtypes, while low risk HPV subtypes are more likely to cause well differentiated tumors, Squamous cell carcinoma is the second most common type of cervical cancer following endocervical adenocarcinoma. 2002 May;2(5):342-50. High-risk oncogenic HPV subtypes have been shown to be capable of transforming oral epithelial cells through the viral oncoproteins E6 and E7. differentiated The separation of verrucous hyperplasia from verrucous carcinoma is often difficult, requiring clinical-pathological confrontation. Most SCCs are moderately-differentiated (Barnes et al., 2005; Thompson, 2006). Clinical-pathological correlation is often needed to make the diagnosis (Barnes et al., 2005). The SCC component can present either as in situ or as an invasive SCC. 2006 Sep 1;12(17):5064-73. The SCC component is usually minor to inconspicuous with the sarcomatoid part dominating. Basal-cell carcinoma cells appear similar to epidermal basal cells, and are usually well differentiated. Hama T, Yuza Y, Saito Y, O-uchi J, Kondo S, Okabe M, Yamada H, Kato T, Moriyama H, Kurihara S, Urashima M. Oncologist. 2007 Dec 20;357(25):2552-61. Infiltrating SCC may be focal, requiring multiple sections for demonstration. Triple-negative breast cancer (TNBC), a specific subtype of breast cancer that does not express estrogen receptor (ER), progesterone receptor (PR), or human epidermal growth factor receptor 2 (HER-2), has clinical features that include high invasiveness, high metastatic potential, proneness to relapse, and poor prognosis. 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) (. 1). It consists of tubular structures that give rise to glands within glands. in press. Basaloid squamous cell carcinoma Basaloid squamous cell carcinoma is a high-grade variant of SCC composed of both basaloid and squamous components (Barnes et al., 2005). Poorly differentiated (figures 7, 8) Grading of SCC depends on how easy it is to recognise the characteristics of squamous epithelium (eg. BSCC requires aggressive multimodality treatment, including radical surgery (including neck dissection), radiotherapy, and chemotherapy (especially for metastatic disease). HPV-16 and -18) (zur Hausen, 2002; Moody et al., 2010). CA Cancer J Clin. In patients with oropharyngeal SCC treated with surgery, the 5-year survival rates for p16-negative and p16-positive patients were 26.8% and 57.1%, respectively (Lassen et al., 2009). 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. The differential diagnosis includes neuroendocrine carcinoma, adenoid cystic carcinoma, and adenosquamous carcinoma. Two thirds occur in industrialized nations. Epub 2010 Jul 1. Squamous cell carcinoma (SCC) usually originates at the origin of the tracheobronchial tree, but more cases are now diagnosed in the periphery of the lung. Keratinizing squamous cell carcinoma of the nasopharynx is morphologically similar to keratinizing squamous cell carcinomas occurring in other head and neck sites. Epub 2008 Jul 31. • Degree of differentiation—Well differentiated (i.e., the neoplastic cell simulates its parent or progenitor cell) or poorly differentiated (i.e., the neoplastic cell is bizarre and “ugly”, as defined by pathologic criteria). Spindle cell carcinoma, also termed carcinosarcoma, pseudosarcoma, polypoid carcinoma, sarcomatoid carcinoma, and spindle cell variant of squamous cell carcinoma, is a rare type of malignant tumor that often grows as an exophytic polypoid lesion (see also Chapter 20). Risk factors for oropharyngeal squamous cell carcinoma (SCC) ... invasive carcinomas are classified as well differentiated, moderately differentiated, poorly differentiated, or undifferentiated. EGFR amplification has been detected in 10-30% of cases (Temam et al., 2007; Sheu et al., 2009). Cancer of the tongue may appear as an ulcer infiltrating deeply and reducing the mobility of the tongue. HNSCCs are immunopositive for cytokeratin cocktails, AE1/AE3 and pancytokeratin. SCC of the floor of the mouth may arise as a red or ulcerated lesion or as a papillary growth. Cancer of the gingiva usually presents as an ulceroproliferative growth. 2009 Mar 15;69(6):2568-76. Some may present with a persistent or non-healing nasal sore or ulcer, a nasal mass, or in advanced cases, proptosis, diplopia, or lacrimation (Barnes et al., 2005; Thompson, 2006). In well-differentiated tumors, no additional stains are usually needed. It can present as an exophytic or polypoid mass, or as poorly defined mucosal induration, frequently with ulceration. Cancer of the buccal mucosa may present as an ulcer with indurated raised margins or as an exophytic growth. Small cystic spaces containing PAS- and Alcian Blue-positive material and stromal hyalinization may be noticed. 2008 Mar 19;100(6):407-20. 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. Papillary squamous cell carcinoma Papillary squamous cell carcinoma (PSCC) is a distinct variant of SCC characterized by an exophytic, papillary growth, and a favorable prognosis. (REVIEW). There is proliferation of stratified squamous epithelium in broad processes with keratin cores and keratin-filled crypts which seem to burrow into bone tissue, but lack obvious cytological features of malignancy. Adenosquamous carcinoma This rare aggressive neoplasm originates from the surface epithelium and is characterized by both squamous cell carcinoma and true adenocarcinoma. CDKN2A (encoding p16) can be inactivated by mutation, homozygous deletion, or promoter hypermethylation (Barnes et al., 2005). The advancing margins are usually broad with a pushing appearance. IARC Press, Lyon. moderately 2009 Apr-May;45(4-5):440-6. 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). P16 immunohistochemistry could serve as a potential surrogate marker (Marur et al., 2010). (REVIEW). The E7 protein binds and inactivates the retinoblastoma tumor suppressor gene product pRB, causing the cell to enter S-phase, leading to cell cycle disruption. Other genes are involved in the pathogenesis of HPV-negative tumors. The SCC component predominates, and is usually moderately-differentiated. Patients with HPV-positive HNSCC tend to be younger and have a lower tobacco and alcohol consumption. The EGFR pathway can be targeted through the use of specific tyrosine kinase inhibitors (TKIs), monoclonal antibodies blocking receptor dimerization, and anti-sense oligodeoxynucleotides or siRNA blocking mRNA expression (Glazer et al., 2009). Two thirds occur in industrialized nations. There are more than 100 subtypes of HPV, some of which are involved in cervical carcinogenesis and have been designated as high-risk HPVs (e.g. Sudbo J, Bryne M, Johannessen AC, Kildal W, Danielsen HE, Reith A. Sudbo J, Kildal W, Johannessen AC, Koppang HS, Sudbo A, Danielsen HE, Risberg B, Reith A. Temam S, Flahault A, Perie S, Monceaux G, Coulet F, Callard P, Bernaudin JF, St Guily JL, Fouret P. Temam S, Kawaguchi H, El-Naggar AK, Jelinek J, Tang H, Liu DD, Lang W, Issa JP, Lee JJ, Mao L. Thariat J, Badoual C, Faure C, Butori C, Marcy PY, Righini CA. The WNT gene family consists of structurally related genes which encode secreted signaling proteins. Survival outcomes are poor (40-50% five-year survival rates) and the treatment is uniformly morbid.
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