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PubMed1976

Ultraviolet light carcinogenesis in hairless mice: cell kinetics during induction and progression of squamous cell carcinoma as estimated by the double-labeling method.

The double-labeling method for studying cell cycle kinetics was applied to uninvolved epidermis of hairless mice (irradiated and unirradiated), and at various stages of ultraviolet light (UVL)-induced squamous cell carcinoma. The growth fraction (GF) was determined by continuous labeling with tritiated thymidine (3HTdR). The data indicate that the double-labeling technique is an acceptable method for studying cell kinetics in UVL-induced squamous cell carcinoma. The GF in normal epidermis (unirradiated and irradiated), hyperplastic epidermis, and lesions of squamous cell carcinoma is 1. The duration of cell generation (Tc) and DNA synthesis (Ts) periods decreased progressively with induction and progression of squamous cell carcinoma. For normal epidermis (irradiated mice) the Tc and Ts were 91 and 6.3 hr, respectively. In the hyperplastic epidermis, the Tc and Ts were reduced to 44 and 4.5 hr, respectively, while even lower values were obtained for the tumor (Tc = 16 hr, Ts = 3.1 hr). The labeling index (LI) in normal epidermis was 7% and increased progressively in hyperplastic epidermis (10%) and squamous cell carcinoma (19%). Epidermal cell differentiation in hyperplastic and tumor tissues appears to have been delayed (GF = 1), since cells above the basal layer, which in normal epidermis keratinize, retain the ability to proliferate, as evidenced by extensive incorporation of [3H]TdR in these cells. The results suggest that tumor production is associated with a progressive shortening of the cell cycle and delayed keratinization of epidermal cells.

Animals↗

PubMed2026

Lung Squamous Cell Carcinoma Harbouring a Novel PAX8::PPARγ Fusion and a FGFR2 Exon 7 Missense Mutation.

Comprehensive molecular profiling is now routinely performed in newly diagnosed non-small cell lung carcinomas (NSCLCs) to identify actionable genomic alterations. Although numerous molecular abnormalities have been described in lung carcinomas, rare and unexpected gene fusions may create significant diagnostic challenges, particularly when they are characteristically associated with tumours of different lineages. To our knowledge, this is the first reported case of a primary lung squamous cell carcinoma harbouring an in-frame PAX8::PPARγ fusion with a concurrent FGFR2 exon 7 missense mutation (p.W290C). An 80-year-old man with a smoking history exceeding 50 years presented with a rapidly enlarging PET-avid right upper lobe pulmonary mass. Bronchial brushing cytology demonstrated a hypercellular malignant neoplasm composed of pleomorphic squamoid cells with hyperchromatic nuclei, dense cytoplasm and extensive necrosis. Cell block material showed squamous morphology and diffuse p40 positivity, supporting squamous differentiation. Reflex next-generation sequencing identified an FGFR2 exon 7 missense mutation (p.W290C; c.870G>C) and targeted RNA fusion analysis demonstrated an in-frame PAX8::PPARγ fusion resulting from a t(2;3)(q13;p25.2) translocation. Because PAX8::PPARγ rearrangements are strongly associated with follicular thyroid neoplasms, extensive clinicoradiologic and immunohistochemical correlation was performed to exclude metastatic thyroid carcinoma. Imaging studies showed no thyroid lesion or residual thyroid tissue, and tumour cells were negative for thyroglobulin, TTF-1 and PAX8. Correlation of the clinical history, radiologic findings, cytomorphology, immunophenotype and molecular profile supported the diagnosis of primary lung squamous cell carcinoma. This case expands the molecular spectrum of lung squamous cell carcinoma and highlights the importance of integrated cytopathologic, immunohistochemical, molecular and radiologic evaluation when unexpected gene fusions are identified in cytology specimens.

FGFR2 exon 7 missense mutation↗

PubMed1992

[The expression of cytokeratin No. 17 in squamous cell cancer of the cervix uteri: an immunohistochemical study of 19 cases].

Monoclonal antibodies E3 against cytokeratin No. 17 were used for immunohistochemical examination of samples from 19 squamous-cell carcinomas of the uterine cervix and 10 cases of squamous-cell metaplasia of the endocervix. The above antibodies selectively labelled reserve cells of the cervical canal mucosa, basal layer of mature metaplastic epithelium and parabasal and basal cells of immature metaplastic squamous epithelium. In large-cell keratinizing, non-keratinizing and small-cell carcinomas, the expression of cytokeratin No. 17 revealed tendency to basal orientation and was in many respects similar to that in metaplastic squamous epithelium. It was suggested that all the squamous-cell carcinomas studied originated from reserve (metaplastic) cells.

Adult↗

PubMedDate not supplied

Sequential cytologic study of the development of squamous cell carcinoma induced in subcutaneously implanted bronchial autograft of dog.

Squamous cell metaplasias and the development of squamous cell carcinomas caused by carcinogenic polycyclic hydrocarbon exposure of the lumen of grafted dog bronchi were followed by cytology, and were correlated to histologically and ultrastructurally observed changes seen in the biopsy specimens at the same time periods. Cytologic specimens showed a progression from mild atypia of squamous metaplastic cells, to moderate atypia, and to marked atypia before the development of invasive squamous cell carcinoma. Histology obtained by the biopsy specimens revealed findings corresponding to these cytologic changes. In the premalignant phase, squamous dysplasia and carcinoma in situ-like changes were also seen. Ultrastructural findings of the epithelium, such as widened intercellular space, increasing tonofilaments, enlarged nuclei with deep indentations, and prominent nucleoli with microsegregation were characteristic changes in the preneoplastic stages. It was concluded that this method of cytology, reflecting histologic and ultrastructural changes, is a useful experimental tool for the comparative study of premalignant lesions in the human bronchus and their early neoplastic stages.

Animals↗

PubMed1975

Differentiation of squamous carcinoma of the larynx as a determinant of prognosis.

The changes seen by light and electron microscopy in the differentiation of squamous carcinoma are described. The grading of the differentiation of squamous carcinomas by overall impression and by quantitative methods are discussed. Reasons are given for retaining the former in the assessment of prognosis. Other differentiating phenomena, particularly retention of basement membrane in the formation of rounded rather than jagged growing edges, are discussed. The differentiating effect of radiation on squamous carcinomas is discussed as a means of assessing the efficacy of the radiation. A similar differentiating effect of bleomycin, a cytotoxic drug, on human squamous carcinoma is described. Using electron microscopical criteria belomycin also increases differentiation of a transplanted, experimental, poorly differentiated squamous carcinoma and human laryngeal carcinoma cells in tissue culture. The significance and possible practical utilization of this phenomenon are discussed.

Bleomycin↗

PubMed1975

Squamous metaplasia in the healing of chronic colonic ulcers of the rat.

Chronic ulcers of the rat colon were produced by a administering a 3 per cent. hydrogen peroxide enema. Twenty-three per cent. of the animals with chronic ulcers had areas of squamous metaplasia at the wound margins which in some cases covered the defect. Electron microscopy revealed some areas similar to epidermis with the four characteristic cell layers. The cells demonstrated many filaments, membrane-coated granules, keratohyalin granules and keratin. The cells were linked by complex of cytoplasmic bridges and frequent desmosomes. Basal cells often displayed large irregular nuclei with double nucleoli. Other areas demonstrated a grossly irregular surface with marked cellular pleomorphism and defects in the basement lamina. The incidence of squamous metaplasia and squamous-cell carcinoma in the colon of man is discussed. The ultrastructural characteristics of squamous metaplasia in the trachea and bronchi is recorded and compared with those of the colon. It is suggested that as neoplasia has been observed to follow experimental metaplastic lesions in the bronchus, a similar ocurrence could take place in the colon as the squamous cells exhibited similar characteristics.

Animals↗

PubMed1979

Syringometaplasia: mucinous and squamous variants.

The eccrine sweat ducts are normally lined by cuboidal epithelial cells which may rarely undergo metaplasia, i.e. syringometaplasia. Two lesions were observed in which eccrine sweat ducts displayed the mucinous and squamous variants of syringometaplasia. The first lesion clinically and histologically appeared to be a plantar wart. Microscopically, it consisted of a central invagination surrounded by marked epidermal acanthosis and hyperkeratosis. The invagination was lined by keratinocytes admixed with mucin-filled goblet cells. The mucin was positive by the Alcian blue (pH 2.5) and mucicarmine stains. Numerous eccrine sweat ducts led into the invagination and were focally lined by the mucin-laden cells. Recognition of mucinous syringometaplasia is important since it may be confused with primary or metastatic adenocarcinoma of the skin. The second lesion occurred on the outer ear and was clinically believed to be chondrodermatitis nodularis helicis. Microscopically, there were many islands of atypical squamous cells within the papillary and reticular dermis. These epithelial islands represented squamous syringometaplasia since many contained central lumina with eosinophilic cuticles and blended with normal ductal structures. It is important not to confuse this metaplastic change with invasive squamous cell carcinoma. Squamous syringometaplasia may be analogous to necrotizing sialometaplasia, a recently described phenomenon which occurs in minor salivary glands.

Adenocarcinoma↗

PubMed2025

Cross-Platform Methylation-Based Site of Origin Classification for Squamous Cell Carcinomas.

Squamous cell carcinomas (SCCs) are one of the most common cancer types and can arise at nearly any anatomic site. Because SCCs are one of the most common metastases, do not have reliable site-specific morphologic or genomic features, and have considerable morphologic and immunohistochemical overlap with urothelial carcinomas, distinguishing between primary and metastatic squamous-appearing tumors can be challenging. This distinction can be critical to clinical management. We present Squamous cell carcinoma Methylation for Origin Site (SquaMOS), a methylation-based classifier to predict site of origin of squamous-appearing carcinomas. Trained on publicly available array-based methylation data from 1062 primary SCCs (from lung, head and neck, cervix, and esophagus) and urothelial carcinomas, SquaMOS predicted site of origin in primary tumors with 96.1% accuracy in an internal test set (n = 458) and 97.4% accuracy in an external test set from 3 institutions (n = 78). On metastatic tumors (n = 51), SquaMOS predictions were 96.1% accurate. SquaMOS was directly applicable to shallow Nanopore sequencing data (CpG probe site coverage, 0.25-2.88×) with an accuracy of 91.7% (n = 36; 100% accurate for high-confidence predictions). When tested on SCCs outside the training set types (n = 15, including 3 metastases to lung), no cases were misclassified as of lung origin, supporting accuracy of lung vs nonlung origin classification for diverse SCC types. Overall, we demonstrate highly accurate performance of the SquaMOS classifier on primary and metastatic tumors from multiple data sources, robust to suboptimal tumor purity. We illustrate transferability of our array-based classifier to low-depth Nanopore sequencing data, a potentially rapid means of site of origin determination in a clinical setting.

Humans↗

PubMed1976

Intramural squamous cell carcinoma of the esophagus.

A case of squamous cell carcinoma arising from an esophageal intramural squamous epithelial cyst is reported. Review of the literature reveals no previous reports of malignant transformation of esophageal cysts, although there have been reports of approximately 64 cases of benign esophageal cysts, and 35 cases of carcinoma arising in esophageal diverticula. In the present case, there was a history of increasing dysphagia for 2 months. Esophagram demonstrated a 4.5-cm concentric narrowing of the proximal esophagus just below the superior esophageal ring. Esophagoscopies revealed an esophageal stricture with intact mucosa, and bronchoscopy showed the lesion to be producing tracheal deviation. Multiple esophageal biopsies revealed mild mucosal hyperplasia with deep submucosal inflammatory changes suggesting an underlying lesion. Despite lack of histologic proof of malignancy, the patient underwent radiation therapy and bleomycin chemotherapy on the basis of the highly suggestive radiographic findings, but died with bilateral bronchopneumonia 6 months after admission. Autopsy demonstrated a 1.5-cm long intramural esophageal squamous epithelial cyst, from which arose a locally invasive squamous cell carcinoma, without mucosal involvement or metastases. There was no demonstrable evidence of any associated esophageal diverticulum.

Aged↗

PubMed1978

Squamous cell carcinoma in situ of the endometrium and fallopian tube as superficial extension of invasive cervical carcinoma.

Five cases of squamous cell carcinoma of the cervix associated with widespread squamous cell carcinoma in situ of the endometrial surface are reported. In one case, carcinoma in situ was also found in one fallopian tube in continuity with the cervicoendometrial lesion. A survey of the literature reveals only 20 cases with similar surface endometrial involvement by cervical squamous cell carcinoma. Of these, the fallopian tubes were involved by an identical lesion in six cases only. Pyometra and cervical stenosis were reported in about 66% of the cases. This rare form of upward cervical cancer extension was present in five of 680 cases (0.7%) of squamous cell carcinoma of the cervix in the file of the Tumor Registry of Magee-Womens Hospital.

Adult↗

PubMed1979

Squamous carcinoma of the colorectum and its genesis.

A case of pure aquamous carcinoma of the rectum is presented, and the literature reviewed. Squamous carcinomas of the colorectum are rare tumours which have clinicopathological features in common with adenocarcinomas. Evidence is presented to support the proposal that most tumours of the large intestine that consist partly or completely of squamous elements arise from areas of squamous differentiation in pre-existing adenomas. The pathogenesis of squamous carcinoma and adenosquamous carcinoma appears to be similar to that of adenocarcinoma.

Adenocarcinoma↗

PubMed1976

Viral-specific humoral immunity to herpes simplex-induced antigens in patients with squamous carcinoma of the head and neck.

Serum antibodies to herpes simplex virus-induced antigens (HSVIA) were quantitated in 122 patients with head and neck squamous carcinoma, 93 patients tumor-free after treatment for these malignant lesions, 27 patients with nonsquamous malignant lesions, 30 heavy smokers, and 36 nonsmokers. Serum IgA anti-HSVIA antibodies were detected in a greater percentage of sera of patients with squamous carcinoma (61 per cent), patients previously treated for these malignant lesions (56 per cent), and heavy smokers (57 per cent) than in patients with nonsquamous malignant lesions (11 per cent) or nonsmokers (8 per cent). Furthermore, titers of these antibodies were higher in patients with squamous carcinoma than in smokers. In patients tumor-free more than three years after treatment, the percentage of positive sera was significantly lower than that in untreated patients and in patients three years or less after treatment. This study demonstrates for the first time a high frequency of antibodies to HSV-induced antigens confined to subjects at high risk of developing head and neck squamous carcinoma and in patients with these malignancies as well as a correlation between the levels of these antibodies and clinical course after treatment.

Alcohol Drinking↗

PubMed1977

The exfoliating epithelial surface of the uterine cervix. IV: Scanning electron microscopical study in invasive squamous carcinoma of human subjects.

The exfoliating epithelial surface of 15 invasive squamous carcinomas of the uterine cervix was investigated with the aid of the scanning electron microscope (SEM). At low magnification (less than or equal to 5,000 X) thirteen tumors presented irregular cobblestone-like structures and the remaining two, irregular intermediate formations (i.e. between cobblestones and mosaics). Cellular overlapping was found in three tumors. At higher magnifications (up to 25,000 X) all 15 tumors showed irregular disorganized structures such as bizarre microvilli with or without fragmented microrugae. Seven tumors had in addition tall finger-shaped protrusions and two rumors crater-like formations covered by irregular microvilli. The SEM structure found in invasive squamous carcinoma differed from the SEM structures earlier reported for the normal squamous or glandular epithelium, squamous metaplasia, dysplasia or carcinoma in situ of the uterine cervix.

Biopsy↗

PubMed1977

Bladder cancer and squamous metaplasia in spinal cord injury patients.

The influence of long-term indwelling urethral catheterization was studied by random bladder and urethral biopsies in 62 spinal cord injury patients. Six patients (10 per cent) had diffuse squamous cell bladder carcinoma, 4 of whom had no tumor visible endoscopically. Five of the patients with cancer were among 25 patients (20 per cent) managed with an indwelling urethral catheter for more than 10 years (average 21 years, range 15 to 30 years). The other cancer patient had been free of the catheter for 27 years after suprapubic cystotomy for 4 years. Gross and microscopic hematuria was associated with cancer. Squamous metaplasia of the bladder was significantly greater in patients who had been catheterized for more than 10 years (80 per cent), compared to those catheterized for less than 10 years (42 per cent) and patients without catheters (20 per cent). Urethral squamous metaplasia increased slightly in long-term catheterization patients. Urinary infection was universal and did not distinguish patients with inflammation, metaplasia or cancer. Therefore, the duration of indwelling catheterization seems to be the major factor in squamous changes in these patients.

Adult↗

PubMed1977

Squamous cell carcinoma of the thymus. An analysis of eight cases.

Eight cases of squamous cell carcinoma of the anterior mediastinum, most likely derived from the thymus, are presented. Seven were male and one female ranging in age from 39 to 65 years; the average was 55.5 years. There were no cases associated with any paraneoplastic syndromes. They possessed common morphological characteristics. Grossly, the tumors resembled malignant thymoma. Invasion of the lung and metastases to regional lymph nodes were frequent. Often observed microscopically were foci of sharply defined keratinization resembling Hassall's corpuscles, no radial arrangement of tumor cells at the periphery of nests, and broad, fibrotic, or hyalinized stroma. Admixture of a few lymphoid cells and some features transitional to thymoma were also observed in some parts of tumors. However, undoubtedly carcinomatous areas were present in some or large parts of all the tumors, where individual cells possessed a vesicular nucleus and a prominent round nucleolus. These features were distinct from those of bronchogenic squamous cell carcinoma and other thymic tumors, although they appeared to be related to thymoma. Treatment of choice is radical surgery and postoperative radiotherapy, because of relatively high radiosensitivity. Prognosis of patients was relatively good. From analyses of cases it is concluded that squamous cell carcinoma of the thymus should be separated from ordinary thymoma of the epithelial type, and that squamous cell carcinoma involving both the thymus and lungs should be carefully examined for the primary site of growth.

Adult↗

PubMed1977

Condyloma acuminatum and squamous carcinoma of the vulva.

Reported is the association of condyloma acuminatum and squamous carcinoma of the vulva in three cases and condyloma followed by squamous dysplasia in a fourth case. This association has previously been reported in both male and female genitalia and in the perianal area. In our four cases, cancer or squamous dysplasia followed long-standing or extensive condyloma, but there was no evidence of transformation from condyloma to carcinoma. In one of the cases, areas of squamous dysplasia occurred in multiple foci within a large condyloma. It is not known whether condyloma acuminatum is a precancerous skin lesions, but long-standing or extensive condylomas should alert one to the possibility of carcinoma.

Adult↗

PubMed1977

Cytochemical and immunologic of women treated for squamous cell carcinoma of the cervix.

A total of 126 individuals were tested for circulating T lymphocyte levels: 10 patients with stage I-III squamous cell carcinoma of the cervix before treatment; 65 women previously treated with radiation for stage I and II squamous cell carcinoma of the cervix; and 51 healthy age-matched controls. Percentages of aneuploid cells and DNA content in vaginal or cervical smears were determined in 94 patients. All patients with squamous cell carcinoma of the cervix had lower ratios and levels of circulating T lymphocytes than healthy controls. Cytologic and cytochemical DNA studies of vaginal and cervical smears revealed that these individuals had high percentages of aneuploid cells in cervical smears as well as high DNA values. Patients with no evidence of dysplasia had increased circulating T lymphocyte levels compared to pretreatment values, a lower number of aneuploid cells, and mean DNA values close to diploid cells. Based on cytologic and quantitative DNA studies of vaginal and cervical smears, postirradiation dysplasia was diagnosed in 17 of 65 women previously treated by radiation for squamous cell carcinoma of the cervix. No difference in the levels of circulating T lymphocytes between women with postirradiation dysplasia and women without this mucosal disorder and no evidence of cancer was found.

Adult↗

PubMed1976

Isoeffect exponents for the production of dose-response curves in squamous cell carcinomas treated between 4 to 8 weeks.

A scattergram diagram was made of controls and failures of treatment of squamous cell carcinoma in the tonsillar fossa on log-log paper coordinates of doses and treatment times. An exclusion line with an exponent of 0.30 was hand-drawn with all failures below the line. The same methodology has been used for the squamous cell carcinomas of the glosso-palatine sulcus and the base of the tongue. Isoeffect curves were obtained for lesions of all sites of the oropharynx with an exponent of 0.30 for the tonsillar fossa, 0.35 for the glossopalatine sulcus, and 0.38 for the base of the tongue. GHOSSEIN, using the least square method, obtained a curve with a slope of 0.33 for the squamous cell carcinomas of the supraglottic larynx. One can conclude that dose equivalents calculated from the equation D = D.T0.33 can be used as a first approximation in the squamous cell carcinomas of the upper respiratory and digestive tract treated between 4 to 8 weeks. It does not mean that a dose given in 4 weeks is clinically equivalent to a dose given in 7 weeks, derived from the isoeffect curve.

Carcinoma, Squamous Cell↗