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PubMed2006

Nomenclature for very superficial squamous cell carcinoma of the skin and of the cervix: a critique in historical perspective.

Squamous-cell carcinoma is the most common of all cancers and it develops in diverse organs of the body, among those being the skin, lung, gastrointestinal tract, and genitourinary tract, the latter including the cervix. Unfortunately, no unanimity exists for naming very superficial squamous-cell carcinoma; it has not been designated in consistent fashion in a single organ, let alone in all of them, thereby resulting in confusion, not only in regard to terminology per se, but concerning matters conceptual, not the least of those being what appellation to apply to that condition when it is encountered histopathologically. This vexing situation is illustrated graphically in the skin by diagnoses for very superficial squamous-cell carcinoma as disparate as solar keratosis (actinic keratosis, senile keratosis), arsenical keratosis, radiation keratosis, Bowen disease, bowenoid papulosis, squamous-cell carcinoma in situ, as well as variations on the theme of "keratinocytic intraepidermal neoplasia" and "dysplasia," and in the cervix by squamous-cell carcinoma in situ, leukoplakia, cervical intraepithelial neoplasia I-III, as well as variations on the theme of "squamous dysplasia ()." What follows now is a recounting of the history of the subject under consideration here, a critique of dizzying, opaque terms and phrases given to that subject, and a proposal for rectifying what currently is a thoroughly untenable situation because the language, and the ideas expressed by it, are impenetrable to physicians and, thereby, are decidedly disadvantageous to patients. There is a need urgently for a single term for very superficial squamous-cell carcinoma in every organ of the body in which it develops, to wit, one that conveys diagnosis in such logical, lucid, comprehensible fashion that it is understandable, readily and immediately, to clinicians. In that way, physicians charged with management of patients can plan therapy rationally.

Carcinoma, Squamous Cell↗

PubMed2004

Eosinophilic dysplasia of the cervix: a newly recognized variant of cervical squamous intraepithelial neoplasia.

A proportion of cervical squamous intraepithelial lesions encountered in surgical pathology practice contain both metaplastic features and some degree of atypia [so-called eosinophilic dysplasia (ED)] that defy classification according to established criteria. To elucidate the nature of these lesions, we compared 44 cases of ED to 20 classic high-grade squamous intraepithelial lesions (HSILs) and 10 squamous metaplasias using a panel of biomarkers and human papillomavirus (HPV) testing. EDs were defined as 1) lack of normal maturation; 2) relatively abundant eosinophilic cytoplasm and distinct cell borders compared with conventional HSIL; 3) mildly to moderately increased nuclear to cytoplasmic ratio; and 4) focal dysplastic nuclei showing nuclear enlargement, hyperchromasia, variable nuclear membrane irregularities, and appreciable nucleoli. Expression of p16 (p16), MIB-1 (Ki-67) labeling index, and HPV DNA detection and typing were performed on each case. The majority of EDs showed more than three atypical cells in an entire lesion but lack of apparent features of HSIL. It was common to find neighboring cervical squamous metaplasia and/or conventional SILs (either HSIL or low-grade squamous intraepithelial lesion [LSIL]). Among the 44 cases, 18 (45%) ED lesions were found to be associated with HSIL, 15 (34%) with LSIL or condylomatous lesions, and 13 (30%) EDs were seen without any SILs in the entire specimens. Area of benign squamous metaplasia was found in all ED cases. High levels of p16 and MIB-1 expression were seen in 41 (93%) of 44 ED cases with degrees of immunoreactivity closely resembling those seen with HSIL. Of 16 EDs tested, 13 (81%) were positive for HPV DNAs. Among 10 HPV-positive cases subtyped, 9 (90%) cases contained intermediate- and/or high-risk HPVs and 1 case contained a novel HPV. In the follow-up of pure ED cases, the majority showed presence of dysplastic lesions of either HSIL or LSIL on either loop electric excision procedures or Papanicolaou test samples after a 6- to 10-week period. Therefore, ED represents an unrecognized and potentially clinically significant subgroup of cervical intraepithelial lesions. Based on the unique histologic appearance of ED, its association in some cases with HSIL, the overall immunohistochemical findings, frequent association of ED with intermediate- and/or high-risk HPV infection, and limited follow-up data, we believe that ED represents a variant of HSIL (CIN 2). Since ED possesses histologic features of both dysplasia and metaplasia, we speculate that it may arise from metaplastic cervical squamous epithelium that has subsequently become infected with intermediate- or high-risk HPV.

Adolescent↗

PubMed1994

Chromosome 9 allele loss occurs in both basal and squamous cell carcinomas of the skin.

Linkage studies of kindreds with the nevoid basal cell carcinoma syndrome and the high frequency of chromosome 9 allele loss in sporadic basal cell carcinomas indicate that chromosome 9 may contain tumor suppressor genes important in the development of sporadic and familial basal cell carcinomas. The recent mapping of the Ferguson-Smith syndrome, which predisposes affected individuals to the development of multiple lesions histologically indistinguishable from squamous cell carcinomas, suggests that tumor suppressor genes on 9q may also be important in the development of squamous cell neoplasms of the skin. Fifty-four non-melanoma skin cancers (24 basal cell carcinomas, 14 squamous cell carcinomas, and 16 cases of Bowen's disease) were examined for loss of heterozygosity on chromosome 9. Allelic loss at one or more loci on chromosome 9 was observed in 14 of 24 basal cell carcinomas, four of 14 squamous cell carcinomas, and three of 16 cases of Bowen's disease. Allelic deletion of one or more 9q markers was seen in 14 basal cell carcinomas, three squamous cell carcinomas, and three cases of Bowen's disease. Five basal cell carcinomas had interstitial deletions and in one the breakpoint mapped within the nevoid basal cell carcinoma syndrome locus. 9p loss occurred in three of nine informative squamous cell carcinomas. Allelic deletion of 9p markers was not seen in 19 basal cell carcinomas and seven cases of Bowen's disease. These findings suggest that chromosome 9 contains one or more tumor suppressor genes important in the development of both basal and squamous cell carcinomas of the skin.

Alleles↗

PubMed1991

The L1 antigen and squamous metaplasia in the bladder.

The L1 antigen was investigated as a marker of squamous differentiation in urothelium using a monoclonal antibody Mac387, and the results were compared with the expression of high molecular weight cytokeratins. L1 antigen was consistently demonstrated in all instances of partial and complete squamous metaplasia and in squamous carcinomas. In contrast, pure transitional cell carcinomas (except one with minor focal staining), adenocarcinomas and normal and hyperplastic urothelium did not label. In a few squamous carcinomas in situ, the pattern of labelling obtained with Mac387 was different from that seen in invasive squamous carcinomas and metaplasias. Compared with high molecular weight cytokeratins, the expression of L1 was more intense in areas of squamous differentiation. L1 expression, as identified by antibody Mac387, may therefore serve as a useful marker of squamous differentiation in urothelial lesions.

Antibodies, Monoclonal↗

PubMed1986

Monoclonal antibodies to various acidic (type I) cytokeratins of stratified epithelia. Selective markers for stratification and squamous cell carcinomas.

We determined the reactivity of two monoclonal antibodies to cytokeratins that are typically expressed in certain stratified epithelia and several human squamous cell carcinomas using immunoblotting techniques and immunofluorescence microscopy. Antibody KS 8.12 reacted specifically with cytokeratin polypeptides nos. 13 and 16, and stained noncornified squamous epithelia in a rather uniform way. The examination of diverse human carcinomas showed all squamous cell carcinomas to be positively stained with this antibody, whereas all adenocarcinomas were negative. Another antibody, KK 8.60, reacted with polypeptides nos. 10 and 11, and uniformly stained the suprabasal layers of the epidermis. In several noncornified squamous epithelia (e.g., tongue, exocervix), in thymus reticulum epithelial cells, and in moderately and well differentiated squamous cell carcinomas this antibody exhibited a nonuniform labeling pattern that allowed the detection of individual cytokeratin-10/11-positive cells scattered throughout the tissue. It is concluded that antibodies KS 8.12 and KK 8.60 represent specific molecular probes for the definition of certain stages of squamous differentiation in normal development as well as in pathological processes such as squamous metaplasia and carcinogenesis. We propose the use of these antibodies in the differential diagnosis of carcinomas and their metastases.

Adenocarcinoma↗

PubMed2006

Invasive squamous cell carcinoma after treatment of carcinoma in situ with 5% imiquimod cream.

Squamous cell carcinoma in situ has the potential to progress to invasive squamous cell carcinoma. This report presents two cases of punch biopsy-proven squamous cell carcinoma in situ, treated with once-daily application of 5% imiquimod cream for 6 weeks. Both patients developed moderate local inflammatory reactions during treatment. The first patient demonstrated clinical clearance of the scalp lesion after treatment. Two months later, he re-presented with a subcutaneous nodule at the same site. Histology was consistent with recurrent squamous cell carcinoma. Five months following excision of the recurrent tumour, he presented with metastatic squamous cell carcinoma to a cervical lymph node. The second patient had low-grade chronic lymphocytic leukaemia and presented with squamous cell carcinoma in situ of the leg that failed to clear clinically after treatment with imiquimod. He presented 4 months later with a focus of invasive squamous cell carcinoma within the lesion.

Administration, Topical↗

PubMed2004

Esophageal papillomatosis complicated by squamous cell carcinoma in situ.

We present a case of esophageal papillomatosis with underlying squamous cell carcinoma in situ. An esophageal lesion resected from a 74-year-old woman demonstrated histological findings characteristic of squamous cell papilloma (fibrovascular core and numerous finger-like projections covered with hyperplastic squamous epithelium) and severe dysplasia characteristic of squamous cell carcinoma. The relation of squamous papilloma and squamous cell carcinoma is discussed. It is suggested that esophageal squamous cell papilloma is a premalignant lesion.

Aged↗

PubMed2005

Perineural spread of squamous cell carcinoma involving the spinal accessory nerve in an immunocompromised organ transplant recipient.

BACKGROUND: Squamous cell carcinoma is the second most common cutaneous malignancy in humans, affecting approximately 200,000 people in the United States each year. In immunocompromised patients, squamous cell carcinoma is the most common skin cancer, and it also tends to behave more aggressively than in immunocompetent patients. OBJECTIVE: We describe an immunocompromised patient, previously treated for a squamous cell carcinoma of the left posterior shoulder, who subsequently developed a cord-like, intraneural metastasis of the spinal accessory nerve. RESULTS: The patient presented with a 3-month history of lancinating pain of the left neck and shoulder. He had been treated previously for a squamous cell carcinoma of the left posterior shoulder, which subsequently recurred twice. On examination, a cord-like mass was palpable along the path of the spinal accessory nerve. Given the aggressive nature of this patient's squamous cell carcinoma, surgical exploration was performed. Frozen-section analysis of the spinal accessory nerve and of the multiple supraclavicular nerves revealed perineural and intraneural squamous cell carcinoma. CONCLUSION: To our knowledge, this is the first reported case of a primary cutaneous squamous cell carcinoma of the trunk or extremity metastasizing to a cranial nerve.

Carcinoma, Squamous Cell↗

PubMed1988

Immunohistochemistry of cytokeratin proteins in squamous and transitional cell lesions of the urinary tract.

Expression of low and high molecular weight cytokeratin proteins was investigated immunohistochemically in a variety of transitional and squamous epithelial lesions of the urinary tract with and without schistosomiasis. The monoclonal antibodies used were CAM 5.2 and NCL5D3 for low, PK 63 and 121 for high, and MAK 6 for a broad range of intermediate molecular weight cytokeratins. On staining with CAM 5.2 and NCL5D3, urothelial hyperplasias (n = 12) and grades 1 (n = 5) and 2 (n = 10) papillary transitional cell carcinomas showed labelling patterns quite distinct from carcinoma in situ (n = 4) and non-papillary grades 2 (n = 6) and 3 tumours (n = 3). Among squamous lesions only focal positivity was obtained in 14 of 22 moderate to poorly differentiated squamous cell carcinomas. By contrast, PK 63 and 121 stained squamous lesions exclusively. MAK 6 stained the whole range of urothelial and squamous lesions with the exception of squamous metaplasias. Polyclonal antikeratin adequately labelled spindle cell areas of high grade tumours. The distinctive staining patterns given by these or similar antibodies may help in the identification of squamous metaplasia and in diagnosing tumours of the urothelium.

Carcinoma, Squamous Cell↗

PubMed1993

Immunohistochemical analysis of p53 expression in anal squamous neoplasia.

AIMS: To determine the pattern of expression of the p53 tumour suppressor gene product in anal squamous neoplasia, and to determine if this could be used as a marker of disease progression. The association between p53 expression and human papillomavirus (HPV) 16 DNA status of the anal lesions was also investigated. METHODS: The presence and localisation of the p53 protein in formalin fixed, paraffin wax embedded specimens of anal squamous epithelium (normal and neoplastic) was examined using immunohistochemical staining with a panel of two monoclonal antibodies (DO-1, DO-7) and one polyclonal antibody (CM-1). Thirty nine normal anal epithelia, 14 anal intraepithelial neoplasia (AIN) grade 1, seven AIN 2, and 20 AIN 3 specimens were obtained from patients without demonstrable invasive disease; twelve AIN 3 specimens adjacent to invasive disease and 34 anal squamous cancers were also examined. Genomic DNA from all 126 specimens was extracted and analysed for HPV 16 DNA using the polymerase chain reaction (PCR). RESULTS: Nuclear p53 was strongly expressed in 67% (23/34) of invasive anal squamous tumours, 75% (9/12) of AIN 3 specimens adjacent to invasive disease, and in 60% (12/20) of AIN 3 specimens obtained from patients without demonstrable invasive disease. Two of the patients in the latter group with positively staining specimens subsequently developed invasive tumours which had staining characteristics similar to those of the AIN 3 specimens. p53 protein was expressed in very low concentrations in low grade AIN and not at all in normal anal squamous epithelium. In those specimens which stained positively for p53, HPV 16 DNA sequences were detected in 69.5% (16/23) of invasive disease, 77.7% (7/9) of AIN 3 adjacent to invasive disease, 75% (9/12) of AIN 3 obtained from patients without demonstrable invasive disease, 33.3% (2/6) of AIN 2, and in 40% (2/5) of AIN 1. There was no significant correlation between p53 immunostaining and HPV 16 DNA status (p < 0.05). CONCLUSIONS: Aberrant expression of the p53 gene product is probably involved in the pathogenesis of anal squamous neoplasia. Long term follow up studies of all patients with AIN are required to determine if this could be used as a marker of likely disease progression from high grade AIN to invasive disease. There does not seem to be an association between the presence or absence of HPV 16 DNA sequences and mutant p53 proteins in anal squamous neoplasia.

Anus Neoplasms↗

PubMed1995

HPV type 16 in conjunctival and junctional papilloma, dysplasia, and squamous cell carcinoma.

AIMS: To clarify the role of human papillomavirus (HPV) infection in the development of papilloma, dysplasia, squamous cell carcinoma, and basal cell epithelioma arising from the eyelids, including the tunica conjunctiva palpebrum (conjunctiva), its junction to epidemis of eyelid skin (junction), and eyelid skin. METHODS: Sixteen cases of papilloma, four of dysplasia, four of squamous cell carcinoma, and 12 of basal cell epithelioma were examined using formalin fixed and paraffin embedded samples. Detection of HPV-DNA was performed by PCR-RFLP and in situ hybridisation (ISH) methods. RESULTS: HPV-16 was detected in 12/16 papillomas (75%), 2/4 dysplasias (50%), and 1/4 squamous cell carcinomas (25%) but in none of the basal cell epitheliomas. No other HPV subtypes were found. ISH assay showed positive signals in only two cases of dysplasia and squamous cell carcinoma. The mean age of HPV-16 positive dysplasia and squamous cell carcinoma cases (81.7 years) was significantly higher than that of HPV-16 positive papilloma cases (p < 0.01). CONCLUSIONS: Based on the presence of HPV-16 in both benign and malignant lesions and the age distribution, it seems likely that HPV-16 alone may be incapable of causing development of conjunctival and junctional dysplasia and squamous cell carcinoma, and that any correlation between the papilloma-squamous cell carcinoma sequence and HPV infection may be due to rare events.

Adult↗

PubMed2004

COPD increases the risk of squamous histological subtype in smokers who develop non-small cell lung carcinoma.

BACKGROUND: Squamous cell carcinoma has a stronger association with tobacco smoking than other non-small cell lung cancers (NSCLC). A study was undertaken to determine whether chronic obstructive pulmonary disease (COPD) is a risk factor for the squamous cell carcinoma histological subtype in smokers with surgically resectable NSCLC. METHODS: Using a case-control design, subjects with a surgically confirmed diagnosis of squamous cell carcinoma were enrolled from smokers undergoing lung resection for NSCLC in the District Hospital of Ferrara, Italy. Control subjects were smokers who underwent lung resection for NSCLC in the same hospital and had a surgically confirmed diagnosis of NSCLC of any histological type other than squamous cell. RESULTS: Eighty six cases and 54 controls (mainly adenocarcinoma, n = 50) were enrolled. The presence of COPD was found to increase the risk for the squamous cell histological subtype by more than four times. Conversely, the presence of chronic bronchitis was found to decrease the risk for this histological subtype by more than four times. Among patients with chronic bronchitis (n = 77), those with COPD had a 3.5 times higher risk of having the squamous cell histological subtype. CONCLUSIONS: These data suggest that, among smokers with surgically resectable NSCLC, COPD is a risk factor for the squamous cell histological subtype and chronic bronchitis, particularly when not associated with COPD, is a risk factor for the adenocarcinoma histological subtype.

Aged↗

PubMedDate not supplied

Oral squamous cell carcinoma in ad libitum-fed and food-restricted Brown-Norway rats.

A high incidence of oral squamous cell carcinoma was present in male and female Brown-Norway rats fed ad libitum or food-restricted dietary formulations. One hundred eight-nine rats were examined from 4 dietary treatment groups: male ad libitum, male food-restricted, female ad libitum, and female food-restricted. The ad libitum treatment groups for both males and females had significantly more cases of oral squamous cell carcinoma than cohort food-restricted groups. In ad libitum rats, 10 of 47 (21%) males and 15 of 47 (32%) females had oral squamous cell carcinoma, whereas only 4 of 47 (9%) males and 5 of 48 (10%) females in the food-restricted groups were similarly affected. The food-restricted rats lived significantly longer than ad libitum cohorts, so the higher incidence of squamous cell carcinoma was not dependent on extended lifespans. In addition to the dietary influence, a significant difference in oral squamous cell carcinoma incidence occurred between various familial lines. Family lines having representatives in both ad libitum and food-restricted groups had lower oral squamous cell carcinoma incidences in the food-restricted group whether comparing affected litters or individuals. Results suggest that the incidence of oral squamous cell carcinoma in our colony of Brown-Norway rats can be influenced by both the dietary treatment group and genetic predilection within certain pedigrees.

Animal Feed↗

PubMedDate not supplied

Squamous cell carcinoma arising in thyroglossal duct remnant cyst epithelium.

The extremely rare occurrence of invasive squamous cell carcinoma arising from normal epithelial lining of a thyroglossal duct remnant cyst is documented by demonstrating the histopathologic transition from normal squamous epithelium to squamous cell carcinoma. The requirements that must be fulfilled to accept a lesion as arising de novo from the epithelial lining are outlined, and all requirements are achieved. The lesion is differentiated from the less rare papillary or papillary-follicular adenocarcinoma of residual thyroid tissue of the thyroglossal duct tract remnants. This is the sixth report in the world literature of invasive squamous cell carcinoma arising from benign thyroglossal remnant squamous epithelium, and the second demonstrating the transition from normal squamous epithelium to invasive squamous cell carcinoma.

Carcinoma, Squamous Cell↗

PubMed1984

In vitro sensitivity and resistance of cultured human squamous carcinoma cells to cis-platinum and methotrexate.

To determine whether resistance to chemotherapy in advanced head and neck squamous cell carcinoma stems from biochemical mechanisms and to assess the potential usefulness of new anticarcinogens, an in vitro test would be highly desirable. In the past 4 years our laboratory has developed methodology to establish squamous carcinoma cell lines in tissue culture from patients with squamous cancer of the head and neck. We used some of these lines to compare the in vitro effects of methotrexate on squamous carcinoma, fibrosarcoma, and melanoma cells. Three of the squamous carcinoma lines were tested for sensitivity to both methotrexate and cis-platinum; all but one squamous carcinoma cell line exposed to methotrexate showed growth inhibition at the physiologically attainable concentration of 10(-7) M. In contrast, a tenfold higher concentration was required to produce similar effects in the melanoma, while no concentration inhibited fibrosarcoma growth. Cis-platinum showed consistent squamous carcinoma cytotoxicity in 10(-5) M and 10(-6) M concentrations. This approach should be useful for determining the relative sensitivity and resistance of head and neck cancers to chemotherapeutic agents in vitro.

Carcinoma, Squamous Cell↗

PubMed1987

Epithelial membrane antigen expression in benign and malignant squamous epithelium of the head and neck.

A distinction between benign, preneoplastic, and malignant tissue, based upon the expression of surface antigens, would provide useful clinical information. Epithelial membrane antigen (EMA) has been reported in squamous cell carcinomas, but not in normal squamous epithelium. Twenty-nine specimens from 15 patients, representative of the spectra of changes seen in squamous cell epithelium from normal through dysplasia to squamous cell carcinoma, were fixed in B-5 and examined with anti-EMA monoclonal antibody in an immunoperoxidase technique. Normal squamous epithelium does express EMA. Squamous cell carcinoma also expresses EMA. Well-differentiated tumors stain more intensely and in greater numbers of cells than less-differentiated tumors. The presence or absence of EMA expression does not distinguish normal squamous epithelium from carcinoma. Investigations of membrane antigen content in fixed tissue must use methods of fixation that preserve antigenicity. While strict quantitation of immunoperoxidase preparations is not possible, quantitative differences in expression may be important.

Carcinoma, Squamous Cell↗

PubMed1989

SCC-RIA in the diagnosis of squamous cell carcinoma of the head and neck.

A reliable circulating tumor marker, appropriate for head and neck malignancy, is not yet available. This manuscript reports the efficacy of using circulating squamous cell carcinoma antigen in evaluating patients with squamous cell carcinoma of the head and neck. Serum samples from 89 patients with squamous cell carcinoma of the head and neck were obtained before treatment and at intervals following treatment. Squamous cell carcinoma antigen levels were determined by radioimmunoassay. Elevated pretreatment serum levels of squamous cell carcinoma antigen were identified in 39 of 89 patients (44%) who had head and neck squamous cell carcinoma. Of the 16 patients evaluated from this group with recurrent or persistent disease, 15 (93.5%) demonstrated elevated levels of squamous cell carcinoma antigen. However, of the 21 evaluable patients who remained disease free, only 10 (48%) had post-therapy levels within the normal range. The possible use of this marker in aiding the clinical follow-up of head and neck cancer patients is discussed.

Adult↗

PubMed1989

Alterations in glycoconjugate expression following malignant transformation of human oropharyngeal squamous mucosa.

Malignant transformation of the squamous mucosa in the human oropharynx may be accompanied by alterations in carbohydrate production. Glycoconjugate expression was assessed by examining lectin-binding patterns and ABH isoantigen expression in human biopsy specimens from nine cases of carcinoma in situ and ten cases of invasive squamous cell carcinoma as well as adjacent normal squamous mucosa. Ten different fluorescein-conjugated lectins were used. Each lectin binds to specific nonreducing end-terminal carbohydrate residues. Wheat germ agglutinin and peanut agglutinin displayed intense cytoplasmic and/or membrane binding in more than 90% of the carcinoma in situ and squamous cell carcinoma specimens. However, only 40% of normal squamous epithelium specimens displayed intense cytoplasmic and/or membrane binding with wheat germ agglutinin and peanut agglutinin. Bandieraea simplicifolia I and Helix pomatia exhibited weak binding in less than 35% of normal and neoplastic tissues. Weak canavalia ensiformis binding was identified infrequently in the superficial layers of normal squamous mucosa, but was not found in neoplastic epithelium. None of the cases displayed binding for Dolichos biflorus, Ulex europaeus I, Sophora japonica, Glycine maximus, or Ricinus communis. Monoclonal antibodies directed against ABH blood group isoantigens showed increased cytoplasmic immunoreactivity for anti-H in dysplastic and neoplastic tissues, when compared with normal squamous mucosa. These findings indicate that wheat germ agglutinin and peanut agglutinin and H isoantigen are useful markers of malignancy in squamoproliferative lesions of the oropharynx, apparently reflecting alterations in expression of N-acetyl-D-glucosamine and galactose-related sugars, which appear following malignant transformation.

ABO Blood-Group System↗