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Effect of cellularity on the sensitivity of detecting squamous lesions in liquid-based cervical cytology.

OBJECTIVE: To evaluate the effect of cellularity on the sensitivity of both screening and diagnosis in a liquid-based cervical sample. STUDY DESIGN: SurePath samples (TriPath Imaging Inc., Burlington, North Carolina, U.S.A.) with known diagnoses were selected, including 18 negative, 16 low grade squamous intraepithelial lesion (LSIL) and 12 high grade squamous intraepithelial lesion (HSIL) cases. Through a serial dilution technique, samples of varying cellularity were prepared. The 275 slides were assigned random numbers and were routinely screened by 1 of 2 senior cytotechnologists, blinded to the reference diagnosis. Specimens with a screening diagnosis of atypical squamous cells of undetermined significance (ASCUS) or higher were reviewed by two pathologists, resulting in a final consensus diagnosis. Using a grid counting system, cellularity was determined for each slide. RESULTS: There was a clear demarcation in sensitivity between specimens with a cellularity of < 5,000 or > or = 5,000 squamous cells. This applied to both the sensitivity for screening and to the final consensus diagnosis. For cases with a reference diagnosis of LSIL+, at a cytotechnologist screening level of ASCUS or greater, sensitivity increased from 72.8% (< 5,000 cells) to 98.1% (> or = 5,000 cells) and for a reference diagnosis of HSIL from 85.7% to 100%, respectively. Similarly, for the consensus diagnosis, sensitivity rose from 78.5% (< 5,000 cells) to 96.6% (> or = 5,000 cells) for LSIL+ and from 82.9% to 100%, respectively, for HSIL. These differences were statistically significant (P < .001). CONCLUSION: A minimum cellularity of 5,000 squamous cells is recommended for SurePath liquid-based cervical preparations.

Carcinoma↗

Glandular and squamous atypia and intraepithelial lesions in atrophic cervicovaginal smears. One institution's experience.

OBJECTIVE: To review the cytologic features and follow-up histologic findings in atrophic cervicovaginal smears with the diagnoses of glandular or squamous atypia or intraepithelial lesion. STUDY DESIGN: A total of 228 cases were included in the study. The selection criteria included: age > 48 years and a diagnosis of either atypical glandular cells (AGC) (51 cases), cellular changes suggestive of human papillomavirus (HPV) infection (S/O HPV, 97 cases), low grade squamous intraepithelial lesion (LSIL) (60 cases) or high grade squamous intraepithelial lesion (HSIL) (20 cases). Follow-up biopsy information was available for 103 cases (45%). RESULTS: From the AGC group, 35 (69%) cases had tissue studies; 14 (40%) cases showed glandular lesions; 5 (14%) showed squamous intraepithelial lesion (SIL) and atypical cells. Follow-up information was available for 32 (33%) cases classified as S/O HPV; significant lesions (glandular/squamous) were found in 11 (34%). In the LSIL category, 22 (37%) cases had follow-up; 16 (73%) showed SIL. In the HSIL category, 14 cases (70%) underwent biopsy, and all showed SIL (four LSIL and nine HSIL) or squamous cell carcinoma. CONCLUSION: Even though atrophy-related epithelial changes often pose diagnostic difficulties in the interpretation of postmenopausal smears, application of reproducible and established cytologic criteria in diagnosing SIL and/or glandular lesions can improve diagnostic accuracy and result in selection of patients for follow-up tissue studies.

Atrophy↗

Proliferation and differentiation characteristics of normal human squamous mucosal cells of the upper aerodigestive tract.

Normal human squamous mucosal cells of the soft palate, buccal surface, epiglottis, hypopharynx, floor of the mouth, and tongue were cultured in vitro in serum-free medium. In medium MCDB 153 containing epidermal growth factor, insulin, bovine pituitary extract, and 0.1 or 2.0 mmol/L Ca++, squamous mucosal cells double every 24 hours. These cells then can be induced to arrest their proliferation reversibly by treatment with transforming growth factor-beta or ethionine, and they can irreversibly growth-arrest during senescence or when cultured in growth factor-deficient medium containing 2 mmol/L Ca++. The latter medium also induces differentiation, as does culture of cells in serum-containing medium. Serum-containing medium furthermore promotes extensive cell stratification and the formation of multilayered squamous mucosal tissue specimens that can be removed intact by Dispase treatment. These specimens represent potential autogenous mucosal grafts that can be used in patients who require reconstructive surgery of the oral cavity and oropharynx. Normal human squamous mucosal cells therefore closely resemble keratinocytes derived from the epidermis in the mechanisms that regulate proliferation and differentiation. This model cell system should facilitate future studies on upper aerodigestive tract squamous mucosal cell physiology and pathophysiology.

Calcium↗

Verrucous squamous cell carcinoma of the larynx: evidence for increased metastatic potential after irradiation.

Verrucous squamous cell carcinoma is a rare type of well-differentiated squamous cell carcinoma with a characteristic morphologic appearance and specific clinical behavior. It has been claimed that this tumor may undergo dedifferentiation after radiotherapy; this will result in a more aggressive behavior. From 1968 to 1980, we have diagnosed and treated 569 squamous cell carcinomas of the larynx. Fourteen of them were reported to exhibit verrucous features macroscopically. These tumors were histopathologically reexamined. All 569 cases were stratified with regard to tumor stage (less than or equal to T2 N0 M0) and treatment (irradiation). Six patients of 340 were then diagnosed as having verrucous squamous cell carcinomas, according to the Ackerman criteria. The patients were followed for at least 5 years and regional metastases of poorly differentiated carcinoma developed in at least two patients in the verrucous carcinoma group within 2 1/2 years after full-dose irradiation. Among the patients with nonverrucous carcinoma, this frequency was estimated to be 3%. This study provides evidence that metastatic spread that occurs after irradiation is approximately 10 times more frequent (p less than 0.05) for T1-2 laryngeal verrucous carcinomas, as compared to the common type of squamous cell carcinoma.

Aged↗

Collision tumor of the thyroid: follicular variant of papillary carcinoma and squamous carcinoma.

BACKGROUND: Collision tumors of the thyroid gland are a rare entity. We present a case of a follicular variant of papillary carcinoma and squamous carcinoma in the thyroid. To the best of our knowledge, this is the first documentation of a collision tumor with a papillary carcinoma and a squamous carcinoma within the thyroid gland. The clinicopathological features and immunohistochemical profile are reported. The theories of origin, epidemiology and management are discussed with a literature review. CASE PRESENTATION: A 65 year old woman presented with a large thyroid swelling of 10 years duration and with swellings on the back and scalp which were diagnosed to be a follicular variant of papillary thyroid carcinoma with metastasis. Clinical examination, radiology and endoscopy ruled out any other abnormality of the upper aerodigestive tract. The patient was treated surgically with a total thyroidectomy with central compartment clearance and bilateral selective neck dissections. The histopathology revealed a collision tumor with components of both a follicular variant of papillary carcinoma and a squamous carcinoma. Immunohistochemical analysis confirmed the independent origin of these two primary tumors. Adjuvant radio iodine therapy directed toward the follicular derived component of the thyroid tumor and external beam radiotherapy for the squamous component was planned. CONCLUSION: Collision tumors of the thyroid gland pose a diagnostic as well as therapeutic challenge. Metastasis from distant organs and contiguous primary tumors should be excluded. The origins of squamous cancer in the thyroid gland must be established to support the true evolution of a collision tumor and to plan treatment. Treatment for collision tumors depends upon the combination of primary tumors involved and each component of the combination should be treated like an independent primary. The reporting of similar cases with longer follow-up will help define the epidemiology, biology and establish standardized protocols for treatment of these extremely rare tumors.

Journal Article↗

Detection of human papillomavirus DNA in normal epithelium and in squamous metaplasia of the uterine cervix by the polymerase chain reaction.

The presence of human papillomavirus (HPV) 16 was studied by using the polymerase chain reaction (PCR) directly on sections histologically defined as normal squamous epithelium and metaplastic squamous tissue of the uterine cervix. Ten specimens of normal epithelium were obtained at hysterectomy from women with uterine leiomyoma. Six specimens of squamous metaplasia were adjacent to the areas of dysplastic epithelium in which HPV 16 DNA had been detected previously by PCR. HPV 16 DNA was amplified specifically and detected in two of 10 normal cervical epithelium specimens and in all of 6 squamous metaplasia specimens adjacent to dysplastic lesions. However, HPV DNA could not be detected in the metaplasia by in situ hybridization. These results suggest that metaplastic squamous tissue adjacent to dysplastic lesions harbors fewer copies of HPV DNA than the dysplastic area and the carcinoma and that the HPV copy number per cell may be relevant to the pathogenesis of cervical carcinoma.

Base Sequence↗

Squamous papillomatosis of the bilateral nasal cavities.

The term "papillomatosis" indicates the tendency towards multicentricity and recurrence that these tumors exhibit (Snyder et al. 1972). A typical squamous papilloma arises from the nasal vestibule and is characterized by the epithelial proliferation growing an exophytic manner. We report a rare case of squamous papillomatosis of the bilateral nasal cavities. A 65-year-old man presented with a 2-year-history of bilateral nasal obstruction. Computed tomographic (CT) scans revealed a soft density mass in the bilateral nasal cavities and ethmoid sinuses. Because the tumors were limited to the nasal cavities and anterior ethmoid sinuses, total removal of the tumors was performed endoscopically. On the basis of the clinicopathological findings, the tumors were diagnosed as squamous papillomas. His post-operative course was uneventful, and he is currently free from disease 13 months after surgery. Nasal papillomas usually arise from the unilateral nasal cavity or paranasal sinus. While some cases of inverted (inverting) papillomas arising from the bilateral nasal cavities have been reported, bilateralism of the nasal squamous papillomas is quite rare. Diagnosis, clinical behavior and treatment of squamous papillomatosis of the bilateral nasal cavities are reviewed.

Aged↗

Prevalence of ulcers of the squamous gastric mucosa in standardbred horses.

This study was performed to determine the prevalence of ulcers in the gastric squamous mucosa in Standardbred racehorses. Observations were performed at monthly intervals between the beginning of their training season and their 1st qualifying race. This study also identified risk factors at different levels of race training. Forty-eight Standardbred racehorses from 3 training stables in Quebec, Canada, were studied. Baseline historical information and gastroscopic findings were recorded at the beginning of the trial, and once a month thereafter, between December 2001 and June 2002, until the horse's 1st qualifying race or the end of the training. Intensity of training ranged from jogging to intensive training just before the 1st race and was assigned an ordinal score. Location of squamous ulcers and their appearance were observed on gastroscopy, and an ordinal score was assigned. Prevalence of squamous ulcers from the 2nd through the 4th month (72-88%) of training remained at a significantly higher level (P = .002 to .04) than at the onset of the study (38%) and was also higher in intensely trained horses than in joggers (93% versus 56%). Moderate or more intensive training increased the odds (odds ratio [OR], 3.39; confidence interval [CI], 1.34-8.56; and OR, 11.4; CI, 3.21-40.5, respectively) of detecting ulcers with higher scores. These odds were also higher in trotters (OR, 2.17; CI, 1.07-4.43) than in pacers and generally increased with the duration of training. Duration of training, training level, and gait type also influenced the number of sites with ulcers in the same way. Ulcers had higher scores along the lesser curvature (LC) and the margo plicatus (MP) areas of the stomach. It was concluded that squamous ulcers appeared early in the training of Standardbred racehorses, that the number of sites affected and the ulcer score are related to the intensity of training, and that trotters are more prone to squamous ulcers than pacers.

Animals↗

Suprasellar squamous papillary craniopharyngioma: a case report.

BACKGROUND: Craniopharyngiomas are benign neoplasms that are usually suprasellar in origin. They are considered a type of pituitary tumor that can cause hyposecretion of anterior pituitary hormones or hypopituitarism. Clinically, they may cause visual and endocrine deficiencies similar to pituitary adenoma. Histopathologically, they are distinct from pituitary adenoma and are generally classified as either adamantinomatous or squamous papillary. Adamantinomatous tumors are more common in children, whereas the squamous papillary type is found almost exclusively in adults. CASE REPORT: A 45-year-old white man came to our clinic with a history of decreased vision in his left eye for the previous five months that fluctuated. Magnetic resonance imaging of the brain revealed a suprasellar multilobular mass, which was distinguishable from the pituitary gland. The patient underwent a right frontotemporal craniotomy for resection of the tumor. Histopathological analysis showed a benign squamous epithelial-lined mass consistent with squamous papillary craniopharyngioma. CONCLUSION: Craniopharyngiomas are generally considered to be adamantinomatous or squamous papillary in origin. Recently, magnetic resonance imaging has been used to distinguish between these two types of tumors, although clinically no significant difference has been found with respect to resectability. Clinical presentation, treatment options, recurrence, and differential diagnosis of craniopharyngiomas are discussed.

Craniopharyngioma↗

Retinoid status and the control of keratin expression and adhesion during the histogenesis of squamous metaplasia of tracheal epithelium.

We induced vitamin A depletion to define early and late changes during the histogenesis of squamous metaplasia of hamster tracheal epithelium. An early change is the "minimal morphological change" (MMC), in which the mucociliary epithelium is separated from the basement membrane by a continuous layer of basal cells. Immunohistochemistry showed an exclusive localization of the keratins K5 and K14 in basal cells of normal and MMC epithelia. At the MMC stage no staining was observed above the basal layer with antibodies to K5, but upon progression of the lesion to a squamous focus all cells from basal to terminally differentiated were positive for K5 and K14. In contrast, when we used antibodies to the keratins K6 or K13 all cells were negative in the normal epithelium and in the MMC epithelium. Successive layers of suprabasal squamous cells found in squamous metaplasia failed to express normal epidermal differentiation marker keratins K1 and K10 but expressed the proliferation marker keratin K6 and the internal stratified epithelium keratin K13, not normally found in the epidermis or in the trachea. Hamster tracheal epithelial cells could be maintained in culture in serum-free medium for at least 4 weeks in the presence of retinoic acid (RA). In non-RA-containing medium, cells from vitamin A-deficient hamsters showed markedly reduced growth and an increase in the expression of keratins K5, K6, K13, and K14. Since our previous work had implicated retinoids in the control of cell adhesiveness, we were interested to find out whether changes in cell adhesion occur in vitamin A-deficient hamster tracheal epithelial cells, compared to normal cells. Functional assays demonstrated that hamster tracheal epithelial cells, obtained from non-RA-treated tracheas or maintained in culture, displayed reduced attachment to laminin, compared to RA-treated cells. Immunofluorescence studies did not show a decrease either in the alpha 6 integrin subunit, which was localized in the basal aspect of basal cells, or in basement membrane laminin. However, the expression of laminin-binding protein 37 decreased as the epithelium changed from pseudostratified to stratified. Therefore, a coordinated pattern of changes in keratin gene expression, as well as in the expression of laminin-binding protein 37, the precursor to the cell surface laminin receptor 67LR, and in adhesive properties takes place in tracheal epithelium when its phenotype changes from mucociliary to the preneoplastic stage of squamous metaplasia.

Amino Acid Sequence↗

[Cytokeratin expression in squamous-cell metaplasia of the cervix uteri: an immunohistochemical study using monoclonal antibodies].

Immunohistochemical study of the exo- and endocervix in squamous metaplasia is performed using EE21-06d monoclonal antibodies revealing simultaneously five cytokeratinous polypeptides characteristic of squamous epithelium, and f-12-19h revealing simultaneously wide spectrum of cytokeratinous polypeptides characteristic of the epithelium various types. PAP method and the reaction of immunofluorescence were used. Monoclonal antibodies 12-19d label cells of all layers of normal exocervix, endocervix and metaplastic squamous epithelium, both immature and differentiated. Monoclonal antibodies EE21-06d react in the exocervix with suprabasal and higher located cells and in the endocervix with reserve cells only. Positive reaction with EE21-06d in the metaplastic foci increases in proportion with the squamous cell differentiation, thus this antibody being the marker of reserve cells and the degree of the squamous metaplasia maturity.

Adult↗

Cell density governs the ability of human bronchial epithelial cells to recognize serum and transforming growth factor beta-1 as squamous differentiation-inducing agents.

Sparse (75 to 2000 cells/cm2) density cultures of normal human bronchial epithelial cells uniformly undergo terminal squamous differentiation when incubated in medium containing serum (fetal bovine serum [FBS]) or transforming growth factor beta-1 (TGF-beta 1). It was found that the cell density of the culture affects the probability that a cell will respond to these differentiation-inducing agents. Thus whereas irreversible inhibition of DNA synthesis occurs in sparse cell-density cultures within 24 hours after exposure, only a transient (less than 36 hours) depression in DNA synthesis was seen in high (more than 10,000 cells/cm2) density cultures. In addition, although phase microscopic image analysis revealed that virtually all of the cells displayed a squamous morphology within 1 hour after exposure to FBS or TGF-beta 1, observations made 48 to 72 hours later showed the presence of clusters of small prolate spheroid-shaped cells surrounded by many involucrin-positive squamous-appearing cells. Only the small cells were capable of DNA synthesis and cell division as determined by autoradiography and time-lapse photomicrographic images. These replicating cells immediately undergo squamous differentiation if they are subcultured and reinoculated at low cell density and incubated in medium supplemented with FBS or TGF-beta 1. Therefore the probability that a human bronchial epithelial cell will be refractive to FBS- or TGF-beta 1 induced terminal squamous differentiation is solely a function of the cell density of the culture.

Autoradiography↗

Abnormal Papanicolaou smears after earlier smears with atypical squamous cells.

From November 1984 to January 1986, 138 women were seen in our cervical clinic with atypical squamous cells in a referring cervical Papanicolaou smear. We obtained a second smear and performed a careful pelvic examination, microscopic examination of the vaginal secretions and endocervical culture for the gonococcus. The time interval between the smear showing atypical squamous cells and the one performed in our clinic ranged from 1 to 12 months. The Papanicolaou smear from 59 (50%) of the 117 women who had it repeated within four months returned abnormal as compared to 5 (24%) of the 21 repeated after four months (P = .04). Of 41 women with persistent atypical squamous cells, 10 (24%) had a clinically detectable vaginal infection, while only 3 (4%) of the 74 women with a normal repeat smear had an infection (P less than .01). These findings suggest an association between cervical cytology showing atypical squamous cells and vaginal infections. Nevertheless, this cytologic diagnosis should not be dismissed lightly since a high percentage of women with atypical squamous cells on cytology are found to have dysplasia on colposcopically directed biopsies. The most appropriate method of evaluating these patients has yet to be determined. If the clinician elects to follow these patients with serial Papanicolaou smears, the ideal interval between smears needs to be defined. Our data suggest that an interval of four to six months would be the most efficient.

Adolescent↗

Polypeptide synthesis in columnar and squamous explants of human uterine cervix.

There were quantitative and qualitative differences in the in-vitro synthesis of 3 polypeptides between squamous and columnar epithelial explants of human cervix. One cross-linked keratin-like polypeptide of mol. wt 50,000 was synthesized and phosphorylated by squamous but not by columnar explants; a second cross-linked keratin-like polypeptide of mol. wt 52,000, which was present in larger amounts in squamous than columnar explants, was both glycosylated and phosphorylated during in-vitro explantation of squamous tissue; a third polypeptide of mol. wt 25,200 which was keratin-like but not cross-linked, was synthesized in squamous-tissue explants but in only 4% of columnar-tissue explants.

Autoradiography↗

Postmenopausal squamous atypia: a spectrum including "pseudo-koilocytosis".

In addition to typical atrophy, the postmenopausal cervix may exhibit a spectrum of epithelial and cellular alterations, including prominent perinuclear halos, nuclear hyperchromasia, variation in nuclear size, and multinucleation. It has not been determined whether such changes, termed postmenopausal squamous atypia (PSA), represent age-related epithelial disturbances or human papillomavirus (HPV)-related low-grade squamous intraepithelial lesions (condyloma). We surveyed 30 cervical biopsies from 26 women over the age of 50 that contained cytoplasmic halos and a spectrum of nuclear alterations, either alone or in association with atrophy. Twenty-three exhibited epithelium with 2- to 3-fold nuclear enlargement, and 18 had moderate or marked nuclear staining intensity. Eleven had a maximum of one or more multinucleated cells in a high-power field. Despite the nuclear alterations, none of the biopsies were positive for HPV by PCR analysis. This is in contrast to 104 of 141 low- and high-grade squamous intraepithelial lesions from a wide age range of women analyzed in the same manner (P = .000006). Features distinguishing PSA from HPV-associated low-grade squamous intraepithelial lesions (condyloma) included less variation in nuclear size and staining intensity, more finely and evenly distributed nuclear chromatin, and greater uniformity of perinuclear halos in PSA. In menopausal or postmenopausal women, PSA should be excluded when considering the diagnosis of a low-grade squamous intraepithelial lesion, specifically if the diagnosis rests on the interpretation of koilocytotic atypia.

Aged↗

Endometrial squamous metaplasia. An unusual response to progestin therapy of hyperplasia.

OBJECTIVE: To report the finding of squamous metaplasia within endometrial glands occurring as a result of progestin therapy of hyperplasia. DESIGN: Case series. Retrospective analysis of two cases from 9235 accessioned endometrial biopsies. SETTING: Hospital-based pathology laboratory processing inpatient and outpatient specimens. PATIENTS: Two women, ages 49 and 34 years, with endometrial hyperplasia without squamous metaplasia who were treated with progestin. RESULTS: Extensive squamous metaplasia was found in endometrial glands following progestin therapy. The post-therapy biopsies also showed progestin-related alterations but no evidence of active hyperplasia. CONCLUSION: Squamous metaplasia in these cases appears to be a consequence of progestin therapy. The absence of hyperplasia in the progestin-treated endometrium suggests that the squamous metaplasia does not represent persistence or progression of the original hyperplastic lesion.

Adult↗

Basaloid squamous carcinoma of the head and neck. Report of a case occurring in the anterior floor of the mouth.

Basaloid squamous carcinoma was initially characterized in 1986, and it has been an uncommon entity, with 86 reported cases occurring in the head and neck. Although histologically associated with squamous cell carcinoma and squamous atypia, basaloid squamous carcinoma has distinctive clinical features. It is frequently diagnosed at an advanced stage, often with distant metastases, and it may be associated with second primary tumors. This tumor most commonly occurs in the base of the tongue, hypopharynx, and larynx. We report a case of basaloid squamous carcinoma that occurred in the anterior floor of the mouth--a distinctly unusual location.

Aged↗

Anal human papillomavirus infection and squamous neoplasia in patients with invasive vulvar cancer.

OBJECTIVE: To test the hypothesis that women with invasive vulvar cancer are at high risk of developing human papillomavirus (HPV)-associated anal squamous neoplasia. METHODS: Forty women (median age 54.5 years; range 25-86) who were being treated or had been treated for invasive vulvar cancer and who had not had radiotherapy to the pelvis or anogenital region underwent anal microendoscopy and biopsy. A second group of 80 women who were similar in age to the study group and had no history of anogenital HPV infection or neoplasia formed the control group. The polymerase chain reaction was used to detect HPV 16 DNA in the vulvar and anal tissue samples from 33 patients in the study group and in the anal biopsies of all controls. RESULTS: A histologic diagnosis of anal HPV infection or squamous neoplasia was made in 19 of 40 biopsies (47.5%) in the study group. These diagnoses consisted of one HPV, two anal squamous intraepithelial lesions (SIL) grade I, 15 and SIL grade III (four of which were associated with invasive anal cancers), and one invasive cancer in the absence of anal SIL. Human papillomavirus 16 DNA was detected in 16 of 33 (48.5%) of anal and 25 of 33 (75%) of vulvar biopsies. In addition, HPV 16 was detected in both the anal and vulvar samples in 13 of 16 cases (81%) of anal SIL III and invasive anal squamous cancer. No evidence of anal SIL was found in the controls, and HPV 16 DNA was identified in only 11 (13.7%) of the anal biopsies in this group. CONCLUSIONS: This study provides further evidence for the etiologic relation between genital and anal squamous neoplasia. Furthermore, it shows that women with vulvar cancer are at high risk of having or developing HPV-associated anal neoplasia, particularly in younger patients (P = .0006; 95% confidence interval 12-34). Routine anal examination should be performed in patients with invasive vulvar cancer.

Anal Canal↗