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[Squamous cell carcinoma in black patients: 80 cases].

INTRODUCTION: Squamous cell carcinoma is a malignant epithelial tumor of the skin, rarely observed in "black" skin. It often complicates an acquired or congenital pre-neoplastic dermatosis. We report on 80 cases of squamous cell carcinoma having occurred in black African patients from Senegal. PATIENTS AND METHODS: We retrospectively analyzed all the medical files of patients followed-up in the department for histologically confirmed squamous cell carcinoma from 1980 to 1999. RESULTS: Eighty cases of carcinoma were collected. The mean age of the patients was of 47 years (range: 1 to 85) and the sex ratio was of 1.35 (46 men and 34 women). A pre-neoplastic dermatosis was identified in 65% the patients. Acquired pre-neoplastic dermatosis was: heat burn scars (15 cases), chronic discoid lupus erythematosus (6 cases) and chronic phagedenic ulcer (4 cases). Pre-neoplastic genodermatoses were: albinism (6 cases), xeroderma pigmentosum (5 cases) and epidermodysplasia verruciformis (1 case). Lesions were multiple and cephalic in patients with genodermatosis. Death due to carcinoma occurred in 8 patients. COMMENTS: This large series of squamous cell carcinoma emphasizes: the rarity of squamous cell carcinomas in black patients and the frequency of its occurrence on acquired pre-existing dermatosis. For many years phagedenic ulcers predominated. Our results show the regression of the latter and its increase on post-burn scars and chronic lupus erythematosus. Pre-neoplastic genodermatoses that determine multiple cancers, usually located on sun-exposed areas and occurring in young patients, are particularly severe.

Adolescent↗

Pigmented squamous cell carcinoma of the conjunctiva. A clinicopathologic ultrastructural study.

The clinical and morphologic features of a pigmented squamous cell carcinoma of the bulbar conjunctiva in a 57-year-old black man are reported. The tumor resembled the more usual epibulbar squamous cell carcinoma but had many melanin containing cells within it. Transmission electron microscopy disclosed melanosomes within squamous epithelium, melanocytes, and macrophages. The only cells within the tumor with morphologic features of a malignant neoplasm were squamous in type. The literature on this rare conjunctival tumor, which has a good prognosis following complete excision, is reviewed. Pigmented squamous cell carcinomas need to be distinguished from the more common nodular melanomas, which have a more ominous outlook.

Carcinoma, Squamous Cell↗

Mixed Merkel cell carcinoma and squamous cell carcinoma of the skin.

Four mixed Merkel cell and squamous cell carcinomas of the skin are described. The patients ranged in age from 74 to 90 years and demonstrated or had a history of previous ultraviolet or infrared damage to the skin, manifested by basal cell carcinoma, squamous cell carcinoma, actinic keratoses, solar elastosis, and erythema ab igne. Light microscopic examination of all 4 cases revealed invasive neoplasms consisting of 2 distinct but admixed cell types. The predominant cell type was consistent with Merkel cell carcinoma and was characterized by scant cytoplasm, a small dark polygonal nucleus with granular chromatin, a high mitotic rate, and cytokeratin 20 positivity. In each case, the Merkel cell component merged with a cytokeratin 20 negative squamous component characterized by abundant eosinophilic cytoplasm, intercellular bridges, and keratinization with focal squamous pearl formation. Immunohistochemical staining patterns were consistent with the usual pattern for that cell type; transitional cells were not demonstrated. The intimate admixture of the 2 antigenically different neoplastic cell types, and common etiologic role of ultraviolet and possibly infrared damage, lend support to the theory that some Merkel cell carcinomas and squamous cell carcinomas may arise from a pluripotent epidermal stem cell.

Aged↗

Cutaneous squamous cell carcinomas consistently show histologic evidence of in situ changes: a clinicopathologic correlation.

Squamous cell carcinoma on sun-damaged skin is a malignant neoplasm that evolves from its inception as squamous cell carcinoma in situ, which is commonly referred to as an actinic keratosis. In this study, we reviewed 1011 squamous cell carcinomas on sun-damaged skin and found that nearly 100% of these lesions contained histopathologic changes consistent with squamous cell carcinoma in situ at the periphery or within the confines of the squamous cell carcinoma. These malignant changes began in single layer areas of the lower epidermis and evolved into the epidermis and dermis.

Adult↗

Current concepts in the treatment of bovine ocular squamous cell tumors.

Usually 10 per cent or fewer of the ocular squamous cell tumors in a Hereford cow herd are true carcinomas. Around 30 per cent of the benign tumors regress spontaneously, and squamous cell carcinomas may arise ab initio without progressing from a grossly visible "precursor" lesion. Differential gross and cytologic features assist in making accurate diagnoses of the disease and determining the treatment. Radiation therapy, immunotherapy, surgery, and, in particular, cryosurgery have been employed successfully in the treatment of bovine ocular squamous cell tumors. RF current-induced hyperthermia is an easily performed, highly effective method for treating small squamous cell tumors, causing regression in over 90 per cent of the cases; surgical removal of similar tumors causes regression in only 46 per cent of the cases. A management protocol for controlling losses due to ocular squamous cell tumors in a Hereford or Simmental cow herd includes: Periodic observation of all susceptible cattle. Hyperthermic treatment of all small tumors; orbital exenteration in cases of large, noninvasive carcinomas on the globe or palpebrae; shipment to slaughter of animals with invasive or metastatic disease. Genetic control through careful record keeping and culling.

Animals↗

Surgical treatment of squamous cell carcinoma of the lower lip: evaluation of long-term results and prognostic factors--a retrospective analysis of 184 patients.

PURPOSE: A retrospective study was undertaken to evaluate the results of surgical treatment of primary squamous cell carcinoma of the vermilion border of the lower lip and to identify parameters of the primary tumor that may predict local recurrence and regional metastasis. PATIENTS AND METHODS: From 1979 through 1992, 184 consecutive patients with a primary squamous cell carcinoma of the lower lip underwent surgical excision as a primary treatment. There were 166 (90.2%) men and 18 (9.8%) women, with a mean age of 66 years. Most cases (92.9%) were stage I tumors. Most of the tumors were well and moderately differentiated squamous cell carcinomas (93.5%). Minimal follow-up was 2 years, with a mean of 56 months. Disease control was achieved in 165 (89.7%) patients. Local recurrence and regional metastasis occurred in 9 (4.9%) and 10 (5.4%) patients, respectively. Local failures were treated successfully by either surgery or radiation therapy. Regional metastases were treated in nine patients by neck dissection, followed in eight cases by radiation therapy. One patient developed distant metastasis. RESULTS: Five- and 10-year overall survival rates were 78% and 61%, respectively, whereas the disease-free survival rates at 5 and 10 years were 86% and 81%, respectively. Multivariate analysis indicated that local recurrence was significantly associated with large tumor size and surgical margins containing squamous cell carcinoma. Increasing tumor thickness, an infiltrative invasion pattern, and perineural invasion were significant prognostic indicators of regional metastasis. CONCLUSION: Surgical treatment for small squamous cell carcinomas of the lower lip has a favorable prognosis. Particular parameters of the primary tumor seem to predict the chance of development of local recurrence and regional lymph node metastasis.

Adult↗

Morphological and immunohistochemical evidence suggesting human papillomavirus (HPV) involvement in oral squamous cell carcinogenesis.

Human papillomavirus (HPV) is an agent responsible for squamous cell tumors (verrucae, condylomata and papillomas) at various sites of the body, the oral cavity included. Due to the recently pointed-out association between these HPV lesions and the squamous cell dysplasias and malignancies in the uterine cervix, in the bronchus and in the larynx, the present work was carried out to assess, whether morphological signs (cytopathic effects of HPV) or HPV antigens could be found in lesions of oral squamous cell carcinomas. Biopsies from 40 cases of oral squamous cell carcinomas were surveyed by light microscopy with special emphasis on the presence of the histopathological features suggesting an HPV lesion, i.e. whether flat, inverted or papillomatous condylomas are present concomitantly with the malignancy. All specimens were also subjected to immunoperoxidase staining with anti-HPV serum to disclose the possible HPV antigens in the lesions. Morphological signs of the flat-type HPV lesion were found in 4 cases (10%), those of an inverted type in 3 cases (7.5%), and those of a papillomatous type in 9 cases (22.5%). Epithelial cells (mostly koilocytes) showing HPV-positive nuclei were disclosed in 5 papillomatous lesions, in 2 inverted lesions and in 1 flat lesion. The results suggest that HPV might be the agent involved in the development of at least certain special types of oral squamous cell carcinomas; albeit further confirmatory evidence with other techniques (DNA hybridization) is still needed.

Adult↗

Association between GSTM1*0 and squamous dysplasia of the esophagus in the high risk region of Linxian, China.

Individuals with specific phase I and phase II enzyme polymorphisms may be at increased risk for squamous cell carcinoma of the esophagus. However, to our knowledge there has been only one previous report that evaluates a potential role for these polymorphisms in increasing risk for preneoplastic squamous lesions of the esophagus. To explore this further, we examined polymorphisms in CYP1A1, CYP2E1, GSTM1 and GSTT1, both independently and in combination, for potential associations with the risk of biopsy-proven squamous dysplasia of the esophagus in asymptomatic adults from Linxian, a high risk region in China. Cases consisted of 56 individuals from an esophageal cancer screening study with an endoscopic biopsy diagnosis of mild or moderate squamous dysplasia. Each case was matched on age (+/- 1 year) and gender to a control. Controls were defined as screening study participants with an endoscopic biopsy diagnosis of normal mucosa or esophagitis. DNA was extracted from frozen cell samples obtained by cytologic balloon examination and genotyped using standard methods. Individuals who were GSTM1 null (homozygous for GSTM1*0) were found to have a tendency for an increased risk of esophageal squamous dysplasia (odds ratio=2.6, 95% CI, 0.9-7.4). No excess risks were observed for inheritance of other putative at risk genotypes CYP1A1*2B, CYP2E1*6 or GSTT1*0. The risk associated with the inheritance of combined genotypes was not significantly different than the risk estimates from the univariate analysis. These results are consistent with the notion that exposure to environmental carcinogens that are detoxified by GSTM1, such as polycyclic aromatic hydrocarbons, may contribute to the etiology of esophageal cancer in Linxian.

Carcinoma, Squamous Cell↗

Intracytoplasmic lumina in squamous epithelial lesions of the oral cavity.

Intracytoplasmic lumina are considered a diagnostic feature of adenocarcinomas and have not been reported in squamous cell carcinomas. We are documenting intracytoplasmic lumina in a case of primary squamous cell carcinoma of the oral mucosa and in the oral squamous mucosa in two cases of graft versus host disease, confirming that intracytoplasmic lumina are also present in squamous epithelia and their tumors. Likely explanations for the presence of intracytoplasmic lumina in non-neoplastic and malignant squamous cells of the oral cavity include multiple differentiation, phagocytosis and immune attack on desmosomes.

Adolescent↗

Polypoid squamous cell carcinoma of the larynx. An immunohistochemical study for ras p21 and cytokeratin.

Polypoid squamous cell carcinoma of the larynx consists of two components, namely, squamous cell carcinoma and sarcomatoid spindle cells. To further investigate the histogenesis of the spindle cell component, we studied two cases of polypoid squamous cell carcinoma of the larynx by immunohistochemistry and ultrastructural analysis. Positive staining for ras oncogene p21 and cytokeratin was demonstrated in both squamous cell carcinoma and spindle cell component. Only the latter component was positive for vimentin. Electron microscopic examination showed well-developed desmosomes in spindle cells. These results suggest that the spindle cell component is epithelial in origin and malignantly neoplastic; it originates from mesenchymal metaplasia or squamous cell carcinoma.

Aged↗

p53, p16 and RB expression in adenosquamous and squamous cell carcinomas of the stomach.

The expression of p53, p16 and RB proteins and their clinicopathologic correlation were investigated in 15 cases of primary gastric adenosquamous carcinoma and 2 cases of squamous cell carcinoma of the stomach. The male to female ratio of the patients was 13:4 and the average age was 55.7 years. None of the cases was early gastric carcinoma, and none of the adenocarcinoma components were of the diffuse or signet ring cell types. Fourteen cases showed metastasis to regional lymph nodes and/or other organs at the time of surgery. The adenocarcinoma component was metastasized to lymph nodes in 12 cases, and both adenocarcinoma and squamous cell carcinoma components were metastasized in three cases. The altered expression of p53 correlated with the advanced stage, but did not correlate with the depth of invasion, lymph node metastasis or recurrence. The altered expression of p16 and RB proteins did not correlate with any of the above clinico-pathologic factors. Both the adenocarcinoma and squamous cell carcinoma components revealed an inverse correlation between the expression pattern of p16 and RB proteins (p < 0.05). This suggests that the two proteins share a role in the carcinogenesis of these tumors. The expression pattern of p53 proteins in the adenocarcinoma and squamous cell carcinoma components was exactly the same in all of the cases. The expression patterns of p16 and RB protein were also identical in most of the cases. The expression patterns of all three proteins in the metastatic lesions were also identical to those in the primary lesions. The fact that the alteration of the three tumor suppressor gene products shares the same pattern suggests that squamous and adenocarcinoma components in the stomach originate from the same or a genetically related clone.

Adult↗

Effects of keratinocyte growth factor on the proliferation and radiation survival of human squamous cell carcinoma cell lines in vitro and in vivo.

PURPOSE: Keratinocyte growth factor (KGF) has potent mitogenic activity on normal epithelial cells and has been found to enhance intestinal crypt cell survival in irradiated mice and to prevent radiation and chemotherapy-induced mucositis in animal models. The purpose of the study reported here is to investigate the effect of recombinant human KGF on the proliferation and survival of human squamous carcinoma cell lines following irradiation. METHODS AND MATERIALS: The level of KGF receptor (KGFR) mRNA in normal Balb/Mk cell line and human head and neck squamous carcinoma cell lines was assessed using a RNase protection assay. The clonogenic assay and MTT assay were used to study the proliferative effects of KGF on human tumor cell lines and Balb/MK cell line in vitro. Effects of KGF on in vivo tumor growth and radiosensitivity were studied in three KGFR-positive human squamous cell carcinoma xenografts (FaDu, Detroit 562 and A431) in nude mice, and a murine KGFR-negative melanoma tumor (B16) in Balb/c mice. RESULTS: Seven of 10 tumor cell lines studied expressed KGFR mRNA. None of these tumor cell lines showed enhanced proliferation when exposed to KGF for 2 days or less. Prolonged exposure to KGF for 7 days or longer resulted in low level stimulation of proliferation in both clonogenic and MTT assays in four of seven KGFR-positive cell lines. Two KGFR-negative cell lines also had a low proliferative response to KGF in a clonogenic assay, but not in the MTT assay. Normal keratinocyte Balb/MK cells, which expressed a moderate level of KGFR mRNA, had a strongly proliferative response to KGF. Its KGF enhancement ratio (KER) of plating efficiency was 24-70 times higher than that of the tumor cells studied (p < 0.001). The KGF-stimulated tumor cell growth was almost completely inhibited by heparin or epidermal growth factor (EGF). There were no significant differences (p > 0.05) in the survival of any of tumor cell lines in the presence or absence of KGF (100 ng/ml) irradiated with doses of 0-15 Gy, and no significant differences (p > 0.05) between the radiobiological parameters D0, Dq, and n number from the SHMT model, alpha, beta, and alpha/beta ratio from the LQ model and SF2 for radiation survival curves for cell lines irradiated in the presence or absence of KGF. Three KGFR-positive human squamous cell carcinoma xenografts in nude mice, and a murine KGFR-negative melanoma tumor in Balb/c mice treated with 1.0 mg/kg of KGF for 3 days grew at the same rate as in untreated mice. CONCLUSION: The recombinant human KGF resulted in little or no stimulation of the proliferation of human head and neck squamous tumor cell lines and did not affect the radiosensitivity of these cell lines in vitro and in vivo. Therefore, KGF may be of clinical value in preventing radiation-induced mucositis and may have the potential to increase the therapeutic index of radiotherapy for treatment of cancers.

Animals↗

Immunohistochemical analysis of cyclooxygenase-2 expression in premalignant and malignant esophageal glandular and squamous lesions in Cixian, China.

Increased cyclooxygenase-2 (COX-2) expression has been observed in both squamous cell carcinoma (SCC) and adenocarcinoma (AC) in Western countries, and COX-2 inhibitors have been considered as potential chemopreventive agents for esophageal cancers. Since chemoprevention often targets the premalignant lesions in high-risk population, it is worthwhile to study COX-2 expression in a spectrum of premalignant and malignant lesions obtained from the high-risk populations. In this study, biopsy samples were taken from 240 subjects identified by screening of the high-risk population in Cixian, China, including 27 normal, 29 with squamous hyperplasia, 84 with dysplasia (31 low grade and 53 high grade), 30 with carcinoma in situ, and 70 with invasive carcinoma (60 SCC and 10 AC). For comparison, tissue samples were also collected from He Lon Jiang Province, a low-risk population in China, including 10 patients with invasive SCC, 20 patients with AC, and 17 patients with Barrett's esophagus. The COX-2 protein expression was examined by immunohistochemistry. Using 10% staining as a threshold, 9 of 10 (90%) invasive SCC from low-risk population were COX-2 positive. However, no positive COX-2 staining was seen on normal, hyperplastic, dysplastic, and in situ squamous lesions from the high-risk population, and only 4 of 60 (6%) invasive SCC exhibited positive COX-2 staining. For glandular lesions, 6 of 10 (60%) AC from high-risk area and 15 of 20 (75%) from low-risk area showed positive COX-2 staining, and 12 of 17 (70%) premalignant Barrett's esophagus were also positive. Our findings show that COX-2 expression various in squamous lesions from high- and low-risk areas, but not in glandular lesions. Additional studies are needed to fully explore the mechanisms that are associated with the different COX-2 immunohistochemical staining patterns in esophageal squamous lesions from low- and high-risk populations.

Barrett Esophagus↗

Detection of canine oral papillomavirus-DNA in canine oral squamous cell carcinomas and p53 overexpressing skin papillomas of the dog using the polymerase chain reaction and non-radioactive in situ hybridization.

Nineteen cutaneous and mucocutaneous papillomas, as well as 29 oral and 25 non-oral squamous cell carcinomas of dogs were analyzed immunohistologically for the presence of papillomavirus (PV)-antigens. Canine oral papillomavirus (COPV)-DNA was detected in formalin-fixed, paraffin-embedded tissues by polymerase chain reaction (PCR) and non-radioactive in situ hybridization (ISH). Furthermore, the expression of the tumor suppressor protein p53 was investigated. PV-antigens were detectable in more than 50% of the oral and cutaneous papillomas, while no PV-antigens could be demonstrated in venereal papillomas. One squamous cell carcinoma was PV-antigen positive. Only two cutaneous papillomas of the head showed a strong p53-specific immunostaining, while overexpressed p53 was detectable in approximately 35% of all squamous cell carcinomas. It was possible to amplify fragments of the E6, E7 and L1 gene by polymerase chain reaction (PCR) from five of eight oral and from five of eight cutaneous papillomas as well as from three oral squamous cell carcinomas. Nine of 10 papillomas showed a strong nucleus-associated hybridization signal typical for COPV-DNA. In three squamous cell carcinomas COPV-DNA was located in nests of the epithelial tumor cells surrounding 'horn pearls' or disseminated in the carcinoma tissue. These observations support the view that COPV may also induce non-oral papillomas in the dog and confirm the opinion that a progression of viral papillomas into carcinomas in dogs may occur.

Animals↗

Primary squamous cell carcinoma of the parotid gland: a case report with electron microscopic findings.

Primary squamous cell carcinoma of the parotid gland is a rare tumor. Histological and ultrastructural features of a primary squamous cell carcinoma arising in the right parotid gland is presented. Light microscopically the tumor consisted of poorly differentiated squamous cell nests. PAS reaction was negative. Ultrastructurally the tumor cells were oval or spindle shaped and the cytoplasmic processes were frequently found. The majority of the tumor cells contained numerous intermediate filaments in their cytoplasm. No secretory granule was found. The desmosomes were well developed. It is known that mucoepidermoid carcinoma may be often misdiagnosed as squamous cell carcinoma. These findings can enable us to distinguish primary squamous cell carcinoma from mucoepidermoid carcinoma of the parotid gland.

Carcinoma, Squamous Cell↗

Histological suggestions of 'paratransformation' in oesophageal squamous cell carcinoma.

We have postulated that oesophageal squamous cell carcinoma arises from multifocal areas and not from one cell, and we present the circumstantial evidence for field carcinogenesis in oesophageal cancer. Among 290 cases examined with oesophageal squamous cell carcinoma, lymphatic permeation or intramural metastasis was evident in 110 cases. Of these carcinomatous transformation of the epithelium adjacent to either lymphatic vessel permeation or intramural metastasis of the squamous cell carcinoma was recognized in six cases. It is considered that the cancer tissue either in the lymphatic vessel or intramural metastasis promotes a malignant transformation of the squamous epithelium over these foci. 'Paratransformation' is therefore thought to be one of the potential models of origin for oesophageal squamous cell carcinoma.

Aged↗

Clinicopathologic characteristics and survival of patients with clinical Stage I squamous cell carcinomas of the thoracic esophagus treated with three-field lymph node dissection.

OBJECTIVE: Clinicopathologic characteristics and survival rates of patients with clinical Stage I tumors treated with three-field lymph node dissection have not been well investigated. This report documents the results of a series of cases of clinical Stage I squamous cell carcinomas treated with this surgical procedure in our institute. METHODS: From January 1988 to March 1997, 326 patients with carcinomas of the thoracic esophagus underwent transthoracic esophagectomy with three-field lymph node dissection. Two hundred and ninety-seven (91%) of these had squamous cell carcinomas. Fifty-seven (18%) patients with clinical Stage I squamous cell carcinomas of the thoracic esophagus were retrospectively reviewed here. RESULTS: Among 57 clinical Stage I squamous cell carcinomas, ten (18%) were diagnosed as T1-mucosal and 47 (83%) as T1-submucosal. Seventy percent of the patients with clinical T1-mucosal tumors had additional primary esophageal lesions. The operative morbidity and in-hospital mortality rates were 63 and 0%, and the overall 1-, 3-, 5-, and 10-year survival rates were 95, 86, 78, and 70%, respectively. Of the 57 tumors assessed pathologically, 12 (21%) were T1-mucosal, 42 (74%) were T1-submucosal, and three (5%) were T2. Nineteen (33%) exhibited lymph node metastasis. The 1-, 3-, 5-, and 10-year survival rates for patients with lymph node metastasis were 90, 79, 73, and 58%, respectively, as compared with 97, 90, 80, and 76, respectively for patients without lymph node metastasis (P=0.24). The accuracy of preoperative staging, based on both wall penetration and the status regarding lymph node metastasis, was 63%. With reference to the 1997 UICC-TNM staging system, 36 (63%) were pStage I, two (4%) were pStage IIA, 18 (28%) were pStage IIB, and three (6%) were pStage IVB. The 1-, 3-, 5-, and 10-year survival rates for patients with pStage I disease were 97, 92, 85, and 81%, respectively. In those with pStage II or IV disease, the values were 91, 76, 65, and 52%, respectively. CONCLUSIONS: Three-field lymph node dissection may be indicated even for patients with clinical Stage I squamous cell carcinoma requiring surgical intervention because this surgical procedure provides for possible cure by removing unsuspected lymph node metastasis.

Aged↗

Transforming growth factor-alpha overexpression in proliferative verrucous leukoplakia and oral squamous cell carcinoma: an immunohistochemical study.

Proliferative verrucous leukoplakia is a unique type of oral leukoplakia that has a high risk of malignant transformation. The aim of this study was to examine the expression of transforming growth factor-alpha in proliferative verrucous leukoplakia, oral squamous cell carcinoma, and normal mucosa. Transforming growth factor-alpha, a potent mitogen, is known to play an important role in various neoplasms including oral squamous cell carcinoma. Immunohistochemical localization of transforming growth factor-alpha in archival paraffin-embedded sections was performed with commercially available monoclonal antibodies. Ten cases each of normal mucosa, proliferative verrucous leukoplakia, and oral squamous cell carcinoma were stained. Quantification of the staining intensity, expressed as the cytoplasmic optical density, was done with the Roche Image Analysis System. The data were statistically analyzed with the one-way analysis of variance and Tukey tests. Notably, the mean cytoplasmic optical density of proliferative verrucous leukoplakia was significantly higher than the mean cytoplasmic optical density of normal mucosa (p < 0.01). The mean cytoplasmic optical density of proliferative verrucous leukoplakia was slightly higher than that of oral squamous cell carcinoma, however, this difference was not significant (p > 0.05). The mean cytoplasmic optical density values demonstrate that increased transforming growth factor-alpha immunoreactivity occurs in proliferative verrucous leukoplakia and oral squamous cell carcinoma relative to normal mucosa.

Adult↗