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PubMed1998

Basaloid squamous carcinoma: a clinical comparison of two histologic types with poorly differentiated squamous cell carcinoma.

Basaloid squamous carcinoma (BSC) of the head and neck has been shown to have a poor prognosis when compared with conventional squamous cell carcinoma (SCC). Pathologically, specimens determined to be BSC can have nearly pure basaloid features (group 1) or a mixture of basaloid and squamous features (group 2). The clinical behavior in these 2 subgroups has not been compared previously. BSC is also commonly confused histologically with poorly differentiated SCC (PDSCC). A retrospective comparison of disease stage at presentation, rate of distant metastasis, rate of local recurrence in those offered surgical resection, and rate of survival is made to compare outcomes of the 2 BSC groups and the PDSCC group. The presence of particular histologic features may be associated with poorer outcomes. Patients with BSC have advanced disease at presentation. Survival in the BSC group was less than half that in the PDSCC groups. Statistical analysis shows the 2 groups to be well matched with regard to stage and site of disease. Presence of neck nodal disease on presentation predicts poor survival. In this study distant metastases occurred in 52% of patients with BSC and in 13% of patients in the PDSCC group. The local recurrence rate is comparable for BSC and conventional SCC, with even early tumors in the BSC group recurring distantly rather than locally or regionally. Considering the high distant metastatic rate of BSC and poorer overall survival rate, a more extensive metastatic survey is indicated in these patients before surgery is recommended. We recommend that patients with a diagnosis of BSC not be included with conventional SCC groups in prospective randomized cancer protocols.

Carcinoma, Basosquamous↗

PubMed2006

Atypical squamous cells-cannot exclude high-grade squamous intraepithelial lesion (ASC-H): a result not to be ignored.

OBJECTIVE: The objective of this study was to determine the risk of a clinically significant lesion associated with the diagnosis of atypical squamous cells-cannot exclude high-grade squamous intraepithelial lesion (ASC-H) on cervical cytology (Pap smear). METHODS: This was a retrospective, observational, descriptive study. A computerized database containing cytologic and histologic information for the health region was used to identify women with a diagnosis of ASC-H on a Pap smear performed between January 1 and December 31, 2002. All pertinent pathology data (cytopathology, histopathology, and surgical specimens) were examined. Patients were excluded if they had a diagnosis of cervical cancer, adenocarcinoma in situ (AIS), or high-grade squamous intraepithelial lesion (HSIL) prior to the index Pap smear. RESULTS: During the study period, 727 of 241 841 Pap smears (0.3%) were reported as ASC-H in 655 patients. Ninety-one patients had a previous diagnosis of cervical cancer, AIS, or HSIL and were excluded from analysis, and 12 patients on review did not have ASC-H. There were no follow-up data for 35 of the remaining 552 patients, leaving 517 patients in the study group. In this group, the rates of histologically proven cervical lesions were 2.9% (15/517) for cervical cancer, 1.7% (9/517) for AIS, and 65.6% (339/517) for HSIL. Women undergoing a procedure that included histological examination were more likely to have a significant lesion discovered. CONCLUSION: The diagnosis of ASC-H on Pap smear is associated with an appreciable risk of clinically significant disease. Patients with an ASC-H Pap smear result should undergo timely colposcopic and histologic assessment to rule out HSIL, AIS, and cervical cancer.

Adult↗

PubMed2003

NF-kappaB is constitutively activated in high-grade squamous intraepithelial lesions and squamous cell carcinomas of the human uterine cervix.

We demonstrate, for the first time, that the transcription factor NF-kappaB is constitutively activated during human cervical cancer progression. Immunohistochemical analysis was done using 106 paraffin-embedded cervical tissue specimens of different histological grades. In normal cervical tissue and low-grade squamous intraepithelial lesions, p50, RelA and IkappaB-alpha were mainly localized in the cytosol, whereas in high-grade lesions and squamous cell carcinomas, p50-RelA heterodimers translocated into the nucleus with a concurrent decrease in IkappaB-alpha protein. By Western blot analysis, p50 and RelA were detectable mainly in the cytosolic and nuclear extracts in normal and cancer tissues, respectively, and cytosolic IkappaB-alpha expression was detectable in normal but not in cancer cervical tissues. NF-kappaB DNA-binding activity increased during cervical cancer progression and the binding complex was mainly composed of the p50-RelA heterodimers as revealed by electrophoretic mobility shift assays. Semiquantitative RT-PCR analysis, however, showed increased levels of IkappaB-alpha mRNA in cancer samples presumably because of feedback regulation as a result of enhanced NF-kappaB DNA-binding activity and a consequent functional activation of NF-kappaB. Further immunohistochemical analysis with an antibody to phospho IkappaB-alpha revealed that phosphorylation occurs mainly in squamous intraepithelial lesions, suggesting that the IkappaB-alpha gets phosphorylated initially and degraded as the tumor progressed.

Base Sequence↗

PubMed2003

E2F modulates keratinocyte squamous differentiation: implications for E2F inhibition in squamous cell carcinoma.

E2F regulation is essential for normal cell cycle progression. Therefore, it is not surprising that squamous cell carcinoma cell lines (SCC) overexpress E2F1 and exhibit deregulated E2F activity when compared with normal keratinocytes. Indeed, deliberate E2F1 deregulation has been shown to induce hyperplasia and skin tumor formation. In this study, we report on a dual role for E2F as a mediator of keratinocyte proliferation and modulator of squamous differentiation. Overexpression of E2F isoforms in confluent primary keratinocyte cultures resulted in suppression of differentiation-associated markers. Moreover, we found that the DNA binding domain and the trans-activation domain of E2F1 are important in mediating suppression of differentiation. Use of a dominant/negative form of E2F1 (E2F d/n) found that E2F inhibition alone is sufficient to suppress the activity of proliferation-associated markers but is not capable of inducing differentiation markers. However, if the E2F d/n is expressed in differentiated keratinocytes, differentiation marker activity is further induced, suggesting that E2F may act as a modulator of squamous differentiation. We therefore examined the effects of E2F d/n in a differentiation-insensitive SCC cell line. We found that treatment with the differentiating agent, 12-O-tetradecanoyl-phorbol-13-acetate (TPA), or expression of E2F d/n alone had no effect on differentiation markers. However, a combination of E2F d/n + TPA induced the expression of differentiation markers. Combined, these data indicate that E2F may play a key role in keratinocyte differentiation. These data also illustrate the unique potential of anti-E2F therapies in arresting proliferation and inducing differentiation of SCCs.

Binding Sites↗

PubMed2006

Cost-effectiveness analysis based on the atypical squamous cells of undetermined significance/low-grade squamous intraepithelial lesion Triage Study (ALTS).

BACKGROUND: The ALTS (atypical squamous cells of undetermined significance [ASCUS] and low-grade squamous intraepithelial lesion [LSIL] Triage Study) suggests that, for women diagnosed with ASCUS, human papillomavirus (HPV) DNA testing followed by referral to colposcopy of only those women with oncogenic HPV (i.e., HPV DNA testing) is as effective at detecting cervical intraepithelial neoplasia (CIN) 3 or cancer (CIN3+) as referring all women with ASCUS for immediate colposcopy. We conducted a cost-effectiveness analysis of the ALTS trial to determine whether HPV DNA testing is a cost-effective alternative to immediate colposcopy or conservative management with up to three cytology examinations. METHODS: Data from the ALTS trial were used in conjunction with medical care costs in a short-term decision model. The model compared the incremental costs per case of CIN3+ detected as measured by the incremental cost-effectiveness ratio (ICER) for the following management strategies for women with ASCUS: immediate colposcopy, HPV DNA testing, and conservative management with up to three cytology examinations. RESULTS: The least costly and least sensitive strategy was conservative management with one repeat cytology examination using a threshold of high-grade squamous intraepithelial lesion (HSIL) for referral to colposcopy. Compared with this strategy, triage to colposcopy based on a positive HPV DNA test result had an ICER of 3517 dollars per case of CIN3+ detected. Immediate colposcopy and conservative management with up to three repeat cytology visits detected fewer cases of CIN3+ and were more costly than HPV DNA testing. Immediate colposcopy became cost-effective at 20,370 dollars compared with HPV DNA testing only if colposcopy and biopsy were assumed to be 100% sensitive. CONCLUSIONS: HPV DNA testing is an economically viable strategy for triage of ASCUS cytology. The less than perfect sensitivity of colposcopy and biopsy needs to be accounted for in future clinical guidelines and policy analyses.

Adult↗

PubMed1986

Squamous cell carcinoma of the gallbladder associated with squamous metaplasia and adenocarcinoma in situ of the mucosal columnar epithelium.

A case of well-differentiated squamous cell carcinoma of the gallbladder is presented. Unlike most previously reported cases, the tumor developed in association with squamous metaplasia as well as dysplastic and in situ adenocarcinomatous changes of the gallbladder epithelium. The significance of these lesions is discussed in relation to the histogenesis of squamous cell carcinoma or adenosquamous carcinoma of this organ.

Adenocarcinoma↗

PubMed1997

Carcinoma of the lung in Okinawa, Japan: with special reference to squamous cell carcinoma and squamous metaplasia.

In Okinawa, a subtropical island in southern Japan, squamous cell carcinoma (SCC), especially the well-differentiated form, is prevalent, while this form is relatively rare in both the mainland and other countries (e.g. United States of America). More patients with SCC from Okinawa, moreover, were positive for human papillomavirus (HPV) DNA by polymerase chain reaction (PCR) (79%), and harbored HPV types 6, 16 and 18, in combination. On the other hand, less than 30% of the mainland patients were positive for HPV DNA by PCR. Those patients who were positive all harbored only one HPV type. Furthermore, in Okinawa, there were a significant number of cases with adenosquamous carcinoma, and they too were positive for HPV DNA. The SCC and the adenocarcinoma cells adjacent to the SCC component in these cases were also positive for HPV DNA, and such adenocarcinoma cells were enlarged in size with relatively wide cytoplasm. The authors postulate that HPV infects adenocarcinoma cells and changes them to enlarged cells, followed by squamous metaplasia. In this report, HPV DNA was transfected to adenocarcinoma cells (cultured cell lines) and this showed that HPV causes squamous metaplasia. In addition, aberrant expression of p53 was demonstrated in a large number of the SCC cases in Okinawa. The enlarged adenocarcinoma cells adjacent to the SCC components in adenosquamous carcinomas also showed aberrant expression of p53. The recent advances in the studies of anti-oncogenes, p53, etc. and oncogenes are outlined. It is to be noted that the molecular mechanisms of carcinogenesis in the lung have been studied in general, classifying lung tumors into two groups, namely, small cell carcinoma (SCLC) and non-small cell carcinoma (NSCLC). However, because human lung cancer is represented by a wide variety of histologic types, molecular genetic studies according to a more detailed histological subclassification is needed.

Adult↗

PubMed2003

Squamous cell carcinoma and mammary abscess formation through squamous metaplasia in Smad4/Dpc4 conditional knockout mice.

Smad4 is a central mediator for TGFbeta signals, which play important functions in many biological processes. To study the role of Smad4 in mammary gland development and neoplasia, we disrupted this gene in mammary epithelium using a Cre-loxP approach. Smad4 is expressed in the mammary gland throughout development; however, its inactivation did not cause abnormal development of the gland during the first three pregnancies. Instead, lack of Smad4 gradually induced cell proliferation, alveolar hyperplasia and transdifferentiation of mammary epithelial cells into squamous epithelial cells. Consequently, all mutant mice developed squamous cell carcinoma and/or mammary abscesses between 5 and 16 months of age. We demonstrated that absence of Smad4 resulted in beta-catenin accumulation at onset and throughout the process of transdifferentiation, implicating beta-catenin, a key component of the Wnt signaling pathway, in the development of squamous metaplasia in Smad4-null mammary glands. We further demonstrated that TGFbeta1 treatment degraded beta-catenin and induced epithelial-mesenchymal transformation in cultured mammary epithelial cells. However, such actions were blocked in the absence of Smad4. These findings indicate that TGFbeta/Smad4 signals play a role in cell fate maintenance during mammary gland development and neoplasia.

Abscess↗

PubMedDate not supplied

HLA-DR antigen expression in squamous epithelial dysplasia and squamous cell carcinoma of the esophagus: an immunohistochemical study.

To clarify the biologic significance of esophageal squamous epithelial dysplasia, especially the similarity to carcinoma in situ, immunohistochemical investigation of HLA-DR antigen expression and lymphocyte infiltration was performed. HLA-DR antigen was expressed in 12 of the 35 invasive carcinomas (34.4%), 23 of the 38 intraepithelial carcinomas (60.5%), 21 of the 50 areas of dysplasia (42.0%) and only 2 of the 625 specimens of non-cancerous squamous epithelium (0.3%). The HLA-DR-positive rate of dysplasia localized continuous to HLA-DR-positive carcinoma was 68.4%, which was significantly higher than that for HLA-DR positive dysplasia localized continuous to HLA-DR negative cancer (11.1%) (p<0.05). In areas of dysplasia and intraepithelial carcinoma, T cell infiltration was significantly increased at the sites of HLA-DR antigen expression (P<0.01). B cell infiltration was also more common in areas of positive expression. These results suggest that HLA-DR antigen is associated with the local immune response to squamous epithelial dysplasia, and that HLA-DR antigen expression may prevent tumor invasion similarly to its role in intraepithelial carcinoma.

Adult↗

PubMed2001

Variables associated with squamous intraepithelial lesions among women with a cytologic diagnosis of atypical squamous cells of undetermined significance.

OBJECTIVE: To identify factors among women with atypical squamous cells of undetermined significance (ASCUS) cytologic diagnosis that are associated with either low grade squamous intraepithelial lesions (LSILs) or high grade squamous intraepithelial lesions (HSILs). STUDY DESIGN: From January 1992 to June 1995, 1,660 women with a diagnosis of ASCUS were followed until the next follow-up appointment after the ASCUS diagnosis. Logistic regression analysis with either LSIL or HSIL at follow-up examination as a dependent variable was done with the following independent variables: patient age, method of follow-up, follow-up time, type of health care coverage and household income. RESULTS: In multivariate analyses, there was a 2.7-fold increase in the odds of LSIL (OR = 2.7, 95% CI = 1.3-5.8) for young women (< or = 25 years), a 2-fold decrease in the odds of LSIL (OR = .5, 95% CI .3-.9) for long time to follow-up (> 18 weeks after ASCUS diagnosis) and an 7.8-fold increase in the odds of LSIL (OR = 7.8, 95% CI = 5.1-11.9) for follow-up by colposcopic biopsy. For the odds of HSIL, there was a 6.8-fold increase (95% CI = 3.2-14.5) for follow-up by colposcopic biopsy as compared to Pap smears and a 3-fold decrease in the odds of HSIL (OR = 3, 95% CI = .1-.7) for high-income women (> $34,857). CONCLUSION: Our findings suggest that among ASCUS patients, younger women and those with shorter follow-up time are more likely to be diagnosed with LSIL. Women with a high income showed a protective association for HSIL. Colposcopic biopsy identified more LSIL and HSIL as compared to repeat Pap smear.

Adult↗

PubMed2003

Histopathologic extent of cervical intraepithelial neoplasia 3 lesions in the atypical squamous cells of undetermined significance low-grade squamous intraepithelial lesion triage study: implications for subject safety and lead-time bias.

Cervical intraepithelial neoplasia 3 (CIN3) is the precursor of mostsquamous carcinomas and serves as a surrogate end point. However, small CIN3 lesions are rarely associated with concurrent invasion. We hypothesized that aggressive follow-up for cytology of atypical squamous cells of undetermined significance (ASCUS) or low-grade squamous intraepithelial lesion (LSIL) leads predominantly to detection of smaller CIN3 lesions than those usually associated with cancer. We assessed this hypothesis in a masked histopathologic review of 330 CIN3 lesions in the ASCUS LSILTriage Study, focusing on ASCUS referrals. ASCUS referrals underwent randomized management [colposcopy for repeat cytology of high-grade squamous intraepithelial lesion (HSIL), colposcopy for oncogenic human papillomavirus (HPV) detection or repeat HSIL, or immediate colposcopy]; then all were followed with repeat cytology for 2 years, followed by colposcopy and aggressive treatment. We assessed all CIN3 lesions qualitatively and measured 39 of them. CIN3 lesions were overwhelmingly small. Compared with enrollment, lesions found at follow-up or exit involved fewer tissue fragments (P < 0.01) and showed less diffuse gland involvement (P = 0.03). CIN3 lesions found postenrollment after HPV testing involved the fewest tissue fragments [versus immediate colposcopy (P = 0.04) or repeat cytology of HSIL (P = 0.02)], and none showed diffuse gland involvement. The median distal-proximal length was 6.5 mm (median replacement of total epithelium = 5%) in the 39 measured cases. We conclude that CIN3 lesions underlying ASCUS or LSIL generally lack features associated with invasion, particularly if managed using HPV testing, suggesting that aggressive management leads to early detection of CIN3 but probably prevents relatively few cancers in screened populations.

Adult↗

PubMed2004

[Squamous cell carcinoma of the ureter arising seventeen years after total cystectomy for squamous cell carcinoma of the bladder: a case report].

We report a case of squamous cell carcinoma of the ureter. A 62-year-old woman had undergone total cystectomy and ileal conduit because of squamous cell carcinoma of the bladder when she was 44 years old. Seventeen years later, she complained of edema and oliguria. Antegrade pyelography and loopography revealed a left ureteral tumor. She underwent left ureterectomy and extirpation of the conduit. Pathological diagnosis was moderately differentiated squamous cell carcinoma of the ureter, pT2. The patient is alive without recurrence or metastasis in the first year after surgery.

Carcinoma, Squamous Cell↗

PubMed2005

Case reports of basaloid squamous cell carcinoma--an aggressive variant of squamous cell carcinoma.

Basaloid squamous cell carcinoma (BSCC) is a high grade variant of Squamous Cell Carcinoma with a predilection for the aero-digestive tract. The typical microscopic features of carcinoma with a basaloid pattern in intimate association with a squamous component helps in diagnosis of this tumour. There are few reports in the Indian literature and we report three cases, including one in the sinonasal region. This study discusses the differential diagnosis of BSCC, as recognition of this tumour may have therapeutic implications.

Carcinoma, Basosquamous↗

PubMed1986

An adenoid squamous carcinoma-forming cell line established from an oral keratinizing squamous cell carcinoma expressing carcinoembryonic antigen.

A neoplastic epithelial cell line, TYS, was isolated from a well-differentiated squamous cell carcinoma expressing carcinoembryonic antigen (CEA) that arose in human oral mucosa. Expressions of CEA and amylase as well as ample tonofilaments were detected in cultured TYS cells. Transplantation of the cells into athymic nude mice resulted in production of adenoid squamous cell carcinoma containing CEA and amylase. Cultivation of TYS cells in the presence of sodium butyrate resulted in suppression of cell growth and production of secretory granules with amylase in the cytoplasm of the cells. When the sodium butyrate-treated cells were transplanted into nude mice, a small mass developed transiently at the inoculation site and then disappeared. This mass was histopathologically interpreted as acinic cell carcinoma with squamoid lesion. These findings suggest that we have established a human adenoid squamous carcinoma cell line presumably derived from a minor salivary gland present in oral mucosa.

Adenoids↗

PubMed1985

[Ultrastructure of squamous epithelium in esophageal dysplasia and squamous cell cancer].

Electron microscopic examination of the oesophageal squamous cell carcinoma revealed the presence in the tumour of both undifferentiated and differentiated squamous cells. Keratinocytes appeared and the signs of keratinization were more pronounced in the cytoplasm of differentiated cells. Dysplastic changes were observed at the periphery of the primary node. Two main variants of dysplasia (dark-cell and clear-cell) were distinguished, this at the ultrastructural level being the reflection of the direction of differentiation and the degree of cell maturity in the dysplastic foci. With the exception of few cases with a cell polymorphism in the foci of a severe dysplasia, dysplastic changes of the squamous epithelium were characterized by a monotonous ultrastructural cell composition. The dysplastic cells were distinguished by a degree of differentiation and high synthetic activity.

Carcinoma, Squamous Cell↗

PubMed1996

Implication of retinoic acid receptor gamma in squamous differentiation and response to retinoic acid in head and neck SqCC/Y1 squamous carcinoma cells.

Nuclear retinoic acid receptors are considered to be the mediators of most of the effects of retinoic acid (RA) on gene expression. To explore the role of RA receptor gamma (RARgamma) in the growth and differentiation of SqCC/Y1 head and neck squamous carcinoma cells, they were transfected with RARgamma sense and antisense expression vectors and stable clones in which RARgamma expression was either increased or blocked were isolated. The growth inhibitory effect of RA in monolayer culture was enhanced in the sense transfectants and decreased in the antisense ones. The ability to form colonies in semisolid medium was abolished by RA in the sense transfectants, while the antisense transfected clones exhibited heterogeneous responses. The expression the squamous differentiation markers cytokeratin K1 transglutaminase type I, and involucrin was increased in the absence of exogenous retinoid in a sense transfected clone and decreased in an antisense transfected clone. RA suppressed squamous differentiation in both types of transfectant. The expression of epidermal growth factor receptor (EGFR) was higher in the antisense and lower in the sense transfectant than in the parental cells and RA decreased EGFR mRNA level in the parental and the sense transfectant but not in the antisense transfectant. In addition activator protein-1 (AP-1) binding activity was decreased by the RA treatment in the sense clones, but not in the antisense ones. These results suggest that RARgamma mediates the effects of RA on the cell growth both in monolayer culture and in semisolid medium possibly through AP-1 suppression.

Base Sequence↗

PubMed2002

Effects of age and human papilloma viral load on colposcopy triage: data from the randomized Atypical Squamous Cells of Undetermined Significance/Low-Grade Squamous Intraepithelial Lesion Triage Study (ALTS).

BACKGROUND: Testing for oncogenic human papillomavirus (HPV) DNA at a 1.0-pg/mL threshold represents a promising approach for colposcopy triage of atypical squamous cells of undetermined significance (ASCUS), but not for low-grade squamous intraepithelial lesions (LSIL). Considering age or viral load could improve colposcopy triage. METHODS: We determined the sensitivity for detecting Cervical Intraepithelial Neoplasia 3 (CIN3) and cancer and the percentage of referrals for colposcopy using HPV testing and repeat thin-layer cytopathology in 2198 women with ASCUS and in 848 women with LSIL enrolled in ALTS from November 1996 through December 1998. We analyzed results by age and at two thresholds for HPV load and repeat cytopathology. RESULTS: For ASCUS, the overall sensitivity of HPV testing at 1.0 pg/mL was 96.1% (95% confidence interval [CI] = 92.8 to 99.5%) and varied minimally with age (range, 93.9% to 97.8%). HPV testing at this threshold would refer 31.2% (95% CI = 28.0% to 34.3%) of women aged 29 years or older as compared with more than 65% of younger women. Among women aged 29 years or older with ASCUS, referral for repeat cytopathology of ASCUS had a sensitivity of 90.9% (95% CI = 81.1% to 100.0%) and would refer 50.1% (95% CI = 46.7 to 53.5%). Among all ASCUS, HPV testing using a 10.0-pg/mL threshold decreased sensitivity to 91.5% and referrals to 41.7%. More than 63% of LSIL would have been referred using any strategy achieving 90% sensitivity. CONCLUSION: For women with ASCUS, HPV testing was highly sensitive for detecting CIN3 and cancer with dramatically fewer referrals of older women. Neither a single HPV test nor repeat cytopathology provides useful triage for women with LSIL.

Adult↗

PubMed2003

Atypical squamous cells of undetermined significance--rule out high-grade squamous intraepithelial lesion: cytopathologic characteristics and clinical correlates.

The significance and clinical management of atypical squamous cells of undetermined significance (ASCUS) on cervical cytologic smears has been an area of much controversy. This study compiled a list of criteria useful in identifying the subset of cases that would be categorized as atypical squamous cells of undetermined significance- rule out high-grade squamous intraepithelial lesion (ASC-H) in the new Bethesda System terminology, which eventuate in a diagnosis of cervical intraepithelial neoplasia (CIN). The cytopathology files at Johns Hopkins Hospital were searched for ASC-H cases from the 3-yr period 1996-1998, which had definitive clinicopathologic follow-up (colposcopy and cervical biopsies). The smears were reviewed, cytomorphologic features studied, and clinical correlations performed. ASC-H was diagnosed in 257 of 45,428 gynecologic smears (0.6%), 72 having had clinicopathologic follow-up. Of these 72 cases, 35 (49%) on follow-up had a negative/reactive diagnosis (NR), whereas 37 (51%) turned out to be CIN [CIN-I-18 (49%) and CIN II and III-19 (51%)]. The significant cytomorphologic differences in the ASC-H category with a CIN follow-up (compared with an NR follow-up) were fewer atypical cells, more often discohesive or seen singly, more monomorphic, a higher nuclear-to-cytoplasmic (N/C) ratio, greater nuclear hyperchromasia, more coarse, unevenly dispersed chromatin, more prominent nuclear membrane irregularities, lack of nucleoli, chromocenters or nuclear grooves, and lack of an inflammatory background. Careful attention to subtle cytomorphologic characteristics may be helpful for a more definitive subdivision of ASC-H terminology into a NR and a CIN diagnosis.

Female↗