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Type specific persistence of high risk human papillomavirus (HPV) as indicator of high grade cervical squamous intraepithelial lesions in young women: population based prospective follow up study.

OBJECTIVES: To investigate the role of human papillomavirus (HPV) in the development of cervical neoplasia in women with no previous cervical cytological abnormalities; whether the presence of virus DNA predicts development of squamous intraepithelial lesion; and whether the risk of incident squamous intraepithelial lesions differs with repeated detection of the same HPV type versus repeated detection of different types. DESIGN: Population based prospective cohort study. SETTING: General population in Copenhagen, Denmark. PARTICIPANTS: 10 758 women aged 20-29 years followed up for development of cervical cytological abnormalities; 370 incident cases were detected (40 with atypical squamous cells of undetermined significance, 165 with low grade squamous intraepithelial lesions, 165 with high grade squamous intraepithelial lesions). MAIN OUTCOME MEASURES: RESULTS of cervical smear tests and cervical swabs at enrollment and at the second examination about two years later. RESULTS: Compared with women who were negative for human papillomavirus at enrollment, those with positive results had a significantly increased risk at follow up of having atypical cells (odds ratio 3.2, 95% confidence interval 1.3 to 7.9), low grade lesions (7.5, 4.8 to 11.7), or high grade lesions (25.8, 15.3 to 43.6). Similarly, women who were positive for HPV at the second examination had a strongly increased risk of low (34.3, 17.6 to 67.0) and high grade lesions (60.7, 25.5 to 144.0). For high grade lesions the risk was strongly increased if the same virus type was present at both examinations (813.0, 168.2 to 3229.2). CONCLUSIONS: Infection with human papillomavirus precedes the development of low and high grade squamous intraepithelial lesions. For high grade lesions the risk is greatest in women positive for the same type of HPV on repeated testing.

Adult↗

Photothermal laser ablation of Barrett's oesophagus: endoscopic and histological evidence of squamous re-epithelialisation.

BACKGROUND: Barrett's oesophagus is acquired by severe gastro-oesophageal reflux and is a premalignant condition. Acid suppression or anti-reflux surgery alone do not cause significant regression of the metaplastic mucosa nor reduce the malignant potential. Recent reports have suggested that the combination of mucosal ablation with acid suppression may result in squamous regeneration. AIMS: To destroy Barrett's mucosa by thermal ablation (in the setting of acid suppression) and so induce squamous regeneration. PATIENTS: Sixteen patients with non-dysplastic Barrett's oesophagus were recruited from a surveillance programme. All had been on a proton pump inhibitor. METHODS: At intervals, non-circumferential areas of columnar mucosa were ablated using the KTP laser. Acid suppression was obtained with 40 mg omeprazole daily. Multiple biopsy specimens were obtained for histological examination from ablated areas. RESULTS: Ablation of all areas of glandular mucosa resulted in squamous regeneration. The number of treatments required depended on the length of the Barrett's segment. In 11 patients there was evidence of squamous regeneration over remaining Barrett's glands (in some of the post-treatment biopsy specimens) whilst in nine patients squamous metaplasia was seen within Barrett's glands. CONCLUSION: Mucosal ablation of Barrett's oesophagus by laser, in the setting of acid suppression, results in squamous regeneration (though some burying of Barrett's glands did occur).

Adult↗

Inverted papilloma of the nasal cavity presenting with massive amounts of squamous metaplastic cells in sputum. A case report.

BACKGROUND: Squamous metaplasic cells are rarely seen in sputum of female nonsmokers. CASE: A 47-year-old female nonsmoker presented with massive amounts of squamous metaplasic cells in sputum and an elevated level of squamous cell carcinoma (SCC) antigen in serum present for months, while no causative lesion was detected either by lung computed tomography or bronchoscopy. The patient was eventually diagnosed as having inverted papilloma in the right nasal cavity. Resection of the tumor brought about disappearance of squamous metaplastic cells in sputum and return of serum SCC antigen to the normal range. CONCLUSION: This case clearly demonstrates that squamous metaplastic cells in sputum can originate in lesions in the nasal cavity, although they are rare. It should be kept in mind that the nasal cavity is a potential site producing squamous metaplastic cells in sputum.

Antigens, Neoplasm↗

A small proline-rich protein, SPRR1, is upregulated early during tobacco smoke-induced squamous metaplasia in rat nasal epithelia.

Small proline-rich proteins, believed to be precursor proteins for the crosslinked envelope formation in cells undergoing squamous differentiation, are encoded by the SPRR genes. To further investigate the role of these proteins, the time course of increased synthesis of SPRR1 mRNA in nasal epithelia of rats exposed to cigarette smoke was determined, and the deduced amino acid sequence of the rat SPRR1 was compared with those of other species. Using the pig homologue (20K) antisense cRNA probe, high levels of SPRR1 transcript were detected by in situ hybridization in squamous epithelia that line the nasal vestibule and hard palate of the rat. Basal cells of both the vestibule and palate contained low levels of the transcript, and increasing amounts were detected in the squamous layers. In rats exposed to 250 mg/m3 (total particulate matter) cigarette smoke 6 h/day for 5 days, the number of small mucous cells increased in the respiratory epithelium of the nasal septum in the early stages of squamous differentiation, but were gradually replaced by squamous metaplastic cells. During this transition, hybridization of the 20K antisense cRNA probe increased in the epithelial and mesenchymal cells, indicating that SPRR1 protein could have roles in cellular differentiation other than as a building block of the crosslinked envelope. Similarly, high levels of SPRR1 transcript were detected in the nasal transitional epithelium lining internal walls and maxilloturbinates that had undergone squamous metaplasia after cigarette smoke exposure. At 5 days after the withdrawal of cigarette smoke exposure, the morphology of the midseptal epithelium returned to that of a pseudostratified mucociliary epithelium and the epithelia lining the maxilloturbinates to that of a transitional epithelium. Accompanying this change in morphology of the tissues, the levels of SPRR1 transcripts significantly decreased in the epithelia. However, in the mesenchyme no significant decrease was observed during this recovery. RNA prepared from the external nose surrounding the nasal vestibule contained a transcript of about 0.9 kb that hybridized to the 20K cDNA probe on Northern blot analysis. DNA sequence analysis of the transcript confirmed the identity as that of the SPRR mRNA with its characteristic repeat encoding the oligopeptide with the general consensus -EPC*PKVP-. However, the rat homologue rSPRR1 contained more repeats of the oligopeptide compared with those of higher mammals such as the rabbit, pig, and human, suggesting a possible inverse relation between number of repeats and evolution development. This finding suggests that the number of repeats in the protein may be redundant; however, the conserved sequence of the peptide indicates that this region is essential for the function of this protein.

Amino Acid Sequence↗

Tissue eosinophilia: a morphologic marker for assessing stromal invasion in laryngeal squamous neoplasms.

BACKGROUND: The assessment of tumor invasion of underlying benign stroma in neoplastic squamous proliferation of the larynx may pose a diagnostic challenge, particularly in small biopsy specimens that are frequently tangentially sectioned. We studied whether thresholds of an eosinophilic response to laryngeal squamous neoplasms provides an adjunctive histologic criterion for determining the presence of invasion. METHODS: Eighty-seven(n = 87) cases of invasive squamous cell carcinoma and preinvasive squamous neoplasia were evaluated. In each case, the number of eosinophils per high power field(eosinophils/hpf), and per 10 hpf in the tissue adjacent to the neoplastic epithelium, were counted and tabulated. For statistical purposes, the elevated eosinophils were defined and categorized as: focally and moderately elevated (5-9 eos/hpf), focally and markedly increased(>10/hpf), diffusely and moderately elevated(5-19 eos/10hpf), and diffusely and markedly increased (>20/10hpf). RESULTS: In the invasive carcinoma, eosinophil counts were elevated focally and /or diffusely, more frequently seen than in non-invasive neoplastic lesions. The increased eosinophil counts, specifically >10hpf, and >20/10hpf, were all statistically significantly associated with stromal invasion. Greater than 10 eosinophils/hpf and/or >20 eosinophils/10hpf had highest predictive power, with a sensitivity, specificity and positive predictive value of 82%, 93%, 96% and 80%, 100% and 100%, respectively. Virtually, greater than 20 eosinophils/10 hpf was diagnostic for tumor invasion in our series. CONCLUSION: Our study suggests for the first time that the elevated eosinophil count in squamous neoplasia of the larynx is a morphologic feature associated with tumor invasion. When the number of infiltrating eosinophils exceeds 10/hpf and or >20/10 hpf in a laryngeal biopsy with squamous neoplasia, it represents an indicator for the possibility of tumor invasion. Similarly, the presence of eosinophils meeting these thresholds in an excisional specimen should prompt a thorough evaluation for invasiveness, when evidence of invasion is absent, or when invasion is suspected by conventional criteria in the initial sections.

Journal Article↗

Mast cells dysregulate apoptotic and cell cycle genes in mucosal squamous cell carcinoma.

BACKGROUND: Mucosal squamous cell carcinoma of the head and neck is a disease of high mortality and morbidity. Interactions between the squamous cell carcinoma and the host's local immunity, and how the latter contributes to the biological behavior of the tumor are unclear. In vivo studies have demonstrated sequential mast cell infiltration and degranulation during squamous cell carcinogenesis. The degree of mast cell activation correlates closely with distinct phases of hyperkeratosis, dysplasia, carcinoma in-situ and invasive carcinoma. However, the role of mast cells in carcinogenesis is unclear. AIM: This study explores the effects of mast cells on the proliferation and gene expression profile of mucosal squamous cell carcinoma using human mast cell line (HMC-1) and human glossal squamous cell carcinoma cell line (SCC25). METHODS: HMC-1 and SCC25 were co-cultured in a two-compartment chamber, separated by a polycarbonate membrane. HMC-1 was stimulated to degranulate with calcium ionophore A23187. The experiments were done in quadruplicate. Negative controls were established where SCC25 were cultured alone without HMC-1. At 12, 24, 48 and 72 hours, proliferation and viability of SCC25 were assessed with MTT colorimetric assay. cDNA microarray was employed to study differential gene expression between co-cultured and control SCC25. RESULTS: HMC-1/SCC25 co-culture resulted in suppression of growth rate for SCC-25 (34% compared with 110% for the control by 72 hours, p < 0.001), and dysregulation of genes TRAIL, BIRC4, CDK6, Cyclin G2 and CDC6 in SCC25. CONCLUSION: We show that mast cells have a direct inhibitory effect on the proliferation of mucosal squamous cell carcinoma in vitro by dysregulating key genes in apoptosis and cell cycle control.

Journal Article↗

Dysplastic Ichthyosis uteri-like changes of the entire endometrium associated with a squamous cell carcinoma of the uterine cervix.

Ichthyosis uteri is an exceedingly rare condition in which the entire surface of the endometrium is replaced by stratified squamous epithelium. Originally described as an endometrial response to iatrogenically-introduced caustic substances, similar changes have since been described in association with a variety of inflammatory conditions of the endometrium. We describe herein a heretofore undescribed example of a moderately differentiated squamous cell carcinoma of the uterine cervix associated with extensive ichthyosis uteri-like changes of the entire adjacent endometrium. Additionally, the squamous epithelium of the latter also showed multifocal changes diagnostic of a low-grade squamous intraepithelial lesion. The potential genesis of this composite of findings is discussed, as is the neoplastic potential of ichthyosis uteri. It is concluded that a squamous cell carcinoma of the cervix extended proximally into the endometrium, and that there was a colonization of a pre-existing ichthyosis uteri by associated human papillomavirus. The possibility of significant cervical pathology should be considered when plaques of squamous epithelium with low grade dysplastic changes are identified in an endometrial biopsy or curettage.

Journal Article↗

Randomized placebo-controlled trial of isotretinoin in chemoprevention of bronchial squamous metaplasia.

PURPOSE: Retinoids have proven chemopreventive efficacy in both preclinical and clinical studies. This trial was designed to confirm the finding of an earlier uncontrolled trial that the synthetic retinoid etretinate had major activity in reversing squamous metaplasia found in the bronchial epithelium of chronic smokers. PATIENTS AND METHODS: We prospectively evaluated 152 smokers with bronchoscopy and obtained biopsies from six sites. Subjects with dysplasia and/or a metaplasia index of greater than 15% were randomly assigned to receive either 1 mg/kg isotretinoin or placebo daily for 6 months. Of 86 subjects randomized (41 isotretinoin, 45 placebo), 69 were reevaluated at the completion of treatment. RESULTS: In the group as a whole, the metaplasia index decreased over time from a mean +/- SE of 35.8% +/- 2.7% at baseline to 28.1% +/- 3.3% at the completion of treatment (P = .01) by repeated measures analysis of variance [ANOVA]); a reduction in the metaplasia index (> 8%) was noted in both isotretinoin and placebo groups (19 of 35 [54.3%] and 20 of 34 [58.8%], respectively). Complete reversal of squamous metaplasia was noted in nine subjects from each group. However, the magnitudes of the mean metaplasia index changes did not differ significantly in the two treatment groups. In both groups, smoking cessation resulted in significant declines in the extent of squamous metaplasia, whereas no significant change in metaplasia index was found among those who continued to smoke. CONCLUSION: Squamous metaplasia was frequently observed in bronchial biopsy samples from chronic smokers. From this study, we conclude that isotretinoin has no effect on squamous metaplasia, a potential intermediate end point of bronchial carcinogenesis. Although determining the exact role of isotretinoin in lung cancer prevention requires further study, the finding that there was a significant decrease in squamous metaplasia in the placebo group emphasizes the critical importance of a placebo-controlled study design in chemoprevention trials using intermediate end points.

Adult↗

Control of growth and squamous differentiation in normal human bronchial epithelial cells by chemical and biological modifiers and transferred genes.

The majority of human lung cancers arise from bronchial epithelial cells. The normal pseudostratified bronchial epithelium is composed of basal, mucous, and ciliated cells. This multi-differentiated epithelium usually responds to xenobiotics and physical injury by undergoing basal cell hyperplasia, mucous cell hyperplasia, and squamous metaplasia. One step of the multistage process of carcinogenesis is thought to involve aberrations in control of the squamous metaplastic processes. Decreased responsiveness to regulators of terminal squamous differentiation may confer a selective clonal expansion advantage to an initiated cell. We studied the effects of endogenous [e.g., transforming growth factor beta 1 (TGF-beta 1) and serum] and exogenous [e.g., 12-O-tetradecanoyl-13-phorbol-acetate (TPA), tobacco smoke condensate, and aldehydes] modifiers of normal human bronchial epithelial (NHBE) cell in a serum-free culture system. NHBE cells are growth inhibited by all of these compounds and induced to undergo squamous differentiation by TGF-beta 1 or TPA. In contrast, lung carcinoma cell lines are relatively resistant to inducers of terminal squamous differentiation which may provide them with a selective growth advantage. Chemical agents and activated protooncogenes (ras,raf,myc) altered the response to endogenous and exogenous inducers of squamous differentiation and caused extended cellular lifespan, aneuploidy, and/or tumorigenicity. The data suggest a close relationship between dysregulation of terminal differentiation pathways and neoplastic transformation of human bronchial epithelial cells.

Bronchi↗

Spindle-cell squamous carcinoma of the esophagus: a tumor with biphasic morphology.

Spindle-cell squamous carcinoma of the esophagus is a rare malignant tumor. It is characterized by a large bulky mass in the middle third of the esophagus with a lobulated surface and local expansion of the esophagus. This lesion may be pedunculated and cause relatively little obstruction despite its bulk. The current view, based on ultrastructure and immunohistochemical evidence, has confirmed that the sarcomatous component of the squamous cell carcinoma originates from mesenchymal metaplasia of squamous cells. On the basis of this evidence and clinical behavior, it seems appropriate to consider carcinosarcoma and pseudosarcoma as equivalents and as variants of squamous cell carcinoma. Four patients with spindle-cell squamous carcinoma, an unusual subset of squamous carcinoma, are described, and the salient radiographic and pathologic features of this disorder's distinctive biphasic morphology are discussed.

Aged↗

Expression of a preprorelaxin-like gene during squamous differentiation of rabbit tracheobronchial epithelial cells and its suppression by retinoic acid.

Squamous cell differentiation in tracheobronchial epithelial cells is accompanied by many biochemical and molecular changes. One of the molecular changes in rabbit tracheal epithelial (RbTE) cells is the differential expression of a squamous cell-specific mRNA encoded by the complementary DNA SQ10. In this study, we sequenced SQ10 complementary DNA and showed that this gene encodes a preprorelaxin-like protein. The DNA sequence of the coding region of SQ10 has 68% identity with the human preprorelaxin mRNA, whereas the deduced amino acid sequence exhibits 46% identity with human preprorelaxin. An antiserum (pepIV-Ab) was raised against a synthetic 22-amino acid oligopeptide of the protein encoded by SQ10. Immunoblot analysis of cellular extracts of squamous-differentiated cells showed that this antiserum reacted with proteins of 22 and 20 kilodaltons, possibly constituting prepro- and proforms of this protein. These proteins were undetectable in undifferentiated RbTE cells. In agreement with these observations, PepIV-Ab specifically stained the cytosol of squamous-differentiated RbTE cells but failed to stain undifferentiated cells. PepIV-Ab recognized a 20 and 16 kilodalton polypeptide in medium conditioned by squamous-differentiated RbTE cells, indicating that the prorelaxin-like protein is secreted. The amino acid sequences of three peptides that were obtained after tryptic digestion of the secreted 16 kilodalton protein were identical to sequences encoded by SQ10. Retinoids which have been shown to inhibit squamous differentiation suppressed the induction of SQ10 protein as well as mRNA in a concentration-dependent manner. The concentration at which retinoic acid caused a 50% inhibition of SQ10 mRNA levels was approximately 5 nM.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

[Expression of telomerase reverse transcriptase in premalignant esophageal squamous dysplasia].

OBJECTIVE: To study the relationship of human telomerase reverse transcriptase (hTRT) and malignant transformation of esophageal dysplasia. METHODS: Telomerase activity and hTRT expression in esophageal dysplasia (n = 47), squamous cell carcinoma (n = 29) and normal esophagus (n = 11) were detected by telomeric repeat amplification protocol (TRAP) and in situ hybridization, respectively. RESULTS: Telomerase activity was detected in none of the 11 cases of normal esophageal tissues (0%) but in 21 of 47 cases (44.7%) of dysplasia, and in 25 of 29 cases (86.2%) of esophageal squamous cell carcinoma. There were statistically significant differences among the telomerase activity in normal esophagus, esophageal dysplasia, and in squamous cell carcinoma (chi(2) = 5.89, P < 0.05; chi(2) = 11.35, P < 0.01). hTRT mRNA was expressed in none of the 11 cases of normal esophageal tissues (0%) but in 23 of 47 cases (48.9%) of dysplasia, and in 24 of 29 cases (82.8%) of esophageal squamous cell carcinoma. There were statistically significant differences among the expression of hTRT mRNA in normal esophagus, esophageal dysplasia, and in squamous cell carcinoma (chi(2) = 6.99, P < 0.01; chi(2) = 7.32, P < 0.01). Significant correlation was found between the telomerase activity and the expression of hTRT mRNA (chi(2) = 57.91, P < 0.001). CONCLUSION: The mRNA expression of hTRT which paralleled to telomerase activity implied that there was a crucial role to play in regulating the activation of telomerase, and was closely related to the malignant transformation of esophageal dysplasia. hTRT might serve as a new, valuable biomarker to detect esophageal squamous cell carcinoma.

Adult↗

The triage of squamous cell abnormalities of cervical cytology by human papilloma virus screening.

OBJECTIVE: The aim of the study was to determine the presence of human papilloma virus (HPV) infection in cervical swabs by the use of the Digene Hybrid Capture assay in a cohort of patients with squamous cell abnormalities found in cervical cytologic screening. MATERIALS AND METHODS: Thirty-four (0.3%) of 1,100 patients who came for their routine cervical cytologic screening and diagnosed as having squamous cell abnormalities were enrolled in the study. Colposcopy-directed biopsy was obtained from all study patients. HPV DNA was sought in cervical swab specimens placed in Digene transport medium by the use of the Digene Hybrid Capture assay. The findings of cervical cytology, colposcopy-directed biopsy and HPV screening were compared. RESULTS: In a total of 34 women who were diagnosed as having squamous cell abnormalities in their routine cervical cytologic screening, 15 women had atypical squamous cell lesions of undetermined significancy (ASCUS), 16 women had low-grade cervical intraepithelial lesions (LGSIL), and three women had high-grade cervical intraepithelial lesions (HGSIL). Five (15%) of these women tested positive for HPV screening in cervical swabs where four women had infection with high-risk and one woman had infection with low-risk subtypes. None of the patients with koilocytotic changes of the squamous cells in the class of LGSIL histopathologically tested positive for HPV screening. In addition, one patient diagnosed as having invasive cervical carcinoma histopathologically tested negative for HPV screening. Atypical vascularization was seen colposcopically in this 37-year-old woman who had ASCUS cytologically. CONCLUSION: HPV screening seems to have value in the triage of patients with ASCUS with no clear advantage to colposcopy-directed biopsy. The routine performance of HPV screening for the triage of patients with squamous cell abnormalities has no advantage over colposcopy-directed biopsy.

Adult↗

Role of glycogen synthase kinase 3 in squamous differentiation of pig airway epithelial cells: A primary study.

To investigate if glycogen synthase kinase 3 (GSK3) is involved in squamous differentiation of airway (tracheobronchial) epithelial cells, primary pig airway epithelial cells were treated with lithium chloride, a highly selective inhibitor of GSK3. Change in morphology of cells was monitored under microscopy, and expression of beta-catenin, phosphorylated GSK3 and involucrin, a squamous differentiation marker, were dectected by Western blotting, while expression of mRNA of another squamous differentiation marker, small proline-rich protein, was detected by RT-PCR. Further, luciferase reporter assay was used to assess the activation of beta-catenin/Tcf signaling. The results demonstrated that lithium was able to induce a squamous morphology of the cells, and to enhance the expression of involucrin and small proline-rich protein mRNA. Moreover, lithium increased inhibitory phosphorylation of GSK3, augmented nuclear translocation of beta-catenin in a dose- and time-dependent manner. Activation of beta-catenin/Tcf signaling was observed after the elevation of squamous differentiation markers. Taken together, these data suggest that GSK3 is possibly involved in squamous differentiation of pig airway epithelial cells.

Journal Article↗

Human papillomavirus type 31 DNA detected in part of the dysplasia but in no part of the squamous metaplasia in a specimen taken from one patient.

Using in situ hybridization, human papillomavirus (HPV 6, 16, 18, 31, 33) DNAs were detected in a cervical severe dysplasia accompanied by squamous metaplasia. It was found that, only HPV 31 DNA was harbored in the cervical severe dysplasia, but HPV DNAs were not identified in a lesion of squamous metaplasia. The in situ hybridization method will be of use, therefore, when dysplasia with squamous metaplasia or other lesions are examined for HPV DNA. In a cervical smear, HPV 31 DNA could be detected on the nuclei of dysplastic cells, so this method is applicable to cervical smears. If squamous metaplasia is to be considered as a precursor lesion to cervical dysplasia, the HPV DNA harbored in the dysplasia must also be detected in the accompanying squamous metaplasia. Our results suggested that not all squamous metaplasias were involved with HPV, as far as we were able to detect using five types of HPV DNA probe.

Adult↗

[Squamous metaplasia of the gastric mucosa associated with an aberrant pancreas].

A squamous metaplasia was found in the superficial regenerative epithelium on the aberrant pancreas tissue (Heinrich type II), situated in the posterior wall of the antrum. The squamous epithelium was positively stained by keratin, according to the PAP method, and intestinal metaplasia also was found surrounding the squamous metaplasia. In this case, it was decided that the squamous metaplasia development was associated with the regenerative change of the superficial ulceration. Squamous metaplasia is extremely rare in the stomach, and thus it was difficult to consider that the adenosquamous cell carcinoma of the stomach had developed from the antecedent squamous metaplasia.

Choristoma↗

Basaloid-squamous cell carcinoma of the bronchus. Report of a case with review of the literature.

Basaloid-squamous cell carcinoma (BSCC) is a variant of squamous cell carcinoma with biphasic basaloid and squamous features. Recognition of BSCC is important because this lesion can be confused with less aggressive lesions, such as adenoid cystic carcinoma. BSCC is typically detected at an advanced stage in smokers, alcoholics, and older individuals; adenoid cystic carcinoma is not associated with smoking or alcohol, and it typically occurs in younger individuals. Approximately 88 cases of BSCC in the upper aerodigestive tract have been recorded since its first description in 1986. We report one case of endobronchial BSCC. Cytologically, both squamous and basaloid features were identified, including elongated, irregular, globular, extracellular, hyaline material. Immunohistochemical studies showed two distinct populations of cells: the squamous component, positive for cytokeratin (AE1 + AE3) and negative for smooth-muscle actin, epithelial membrane antigen, S100 protein, and type IV collagen; and the basaloid component, positive for all of the above markers, with minimal staining for cytokeratin (AE1 + AE3). The electron microscopy demonstrated desmosomes in the squamous component and replication of the basal lamina in the basaloid component. We conclude that BSCC of the bronchus is similar to BSCC in the upper aerodigestive tract and should be regarded as a distinct entity.

Actins↗

Histocytological study of squamous atypia on Pap smears.

UNLABELLED: The significance of squamous atypia on Pap smears is currently unclear and its management is controversial. We undertook this study to determine whether cytological parameters on Pap smears with a diagnosis of squamous atypia could be useful in predicting the presence of a squamous intraepithelial lesion (SIL). METHODS: For a 3-mo period, all patients who had a colposcopically directed biopsy and or endocervical curettage (ECC) with a simultaneous or a previous Pap smear showing squamous atypia were identified. All biopsies were reviewed and all cytological smears were evaluated for the following cytological parameters: inflammation, parakeratosis, atypical parakeratosis, number of atypical cells, nuclear size, chromatin pattern (fine, coarse, or hyperchromatic), as well as presence of metaplasia, nuclear membrane irregularity, multinucleation, and nuclear halo in the atypical cells. RESULTS: a total of 97 patients were eligible for the study. The average interval between the Pap smear and colposcopy was 96 days (range, 0 to 364 days). Thirty patients (31%) had SIL on biopsy or ECC, of which 17 (18%) were SIL, low grade, and 13 (13%) were SIL, high grade. Of the 67 that showed no SIL on histology, 24 had inflammatory reactive changes, five had squamous metaplasia with atypia, one had parakeratosis, and 37 had essentially normal biopsies. Most of the cytological features, except coarse chromatin, were equally predictive of SIL with approximately 30% of the patients with any particular feature showing SIL on histology. However, 46% (17/37) of those that had coarse chromatin showed SIL on histology (P < 0.02). Based on this study, squamous atypia on Pap smears appears a marker of an underlying SIL in a considerable number of cases, and coarse chromatin seems most helpful in predicting the presence of SIL.

Adolescent↗