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Morphometric grading of squamous cell carcinoma.

Histological grading of squamous cell carcinoma is subjective and suffers from poor observer reproducibility. We investigated the feasibility of quantifying histological differentiation via point counting, using both the degree of keratinization and a novel definition of differentiation that was based on architectural features of the tumour. Multiple recounts of 20 cases of human oral squamous cell carcinoma were performed at several magnifications (X100, X160 and X250). Six lines of human squamous cell carcinoma tumour lines were examined for changes in differentiation following transplantation to athymic nude mice. Observer reproducibility was extremely high for all recounts except at the highest magnification, where the tumour architecture may have been obscured. Of the human squamous cell carcinomas transplanted to nude mice, five of six tumour lines showed significant histological changes, most commonly toward decreased differentiation. The changes were usually present in the initial transplant and were similar to those we have reported for transplants of adenocarcinomas. We conclude that histological differentiation can be quantified in squamous cell carcinomas with a high degree of observer reproducibility, even in the absence of keratinization; the method employed is sufficiently sensitive to be applied to practical problems of biological significance.

Animals↗

Squamous cell carcinoma in Kauai, Hawaii.

BACKGROUND: It is estimated that over 100,000 new cases of squamous cell carcinoma are diagnosed in the United States annually. This number is compounded by an increasing concern over the ozone layer depletion and the continued sunbathing behavior of many individuals. This could be particularly acute in Hawaii, which may have the highest rates of skin cancer in the country. We believe the updated information on skin cancer is essential to address the magnitude of the problem. METHODS: A prospective 5-year population-based incidence study was conducted on Kauai, Hawaii, between 1983 and 1987 to investigate the frequency of squamous cell carcinomas in resident Caucasians. RESULTS: A total of 58 residents, 37 men and 21 women, were identified with an initial episode of squamous cell carcinoma during the 5-year period. The average annual incidence rate per 100,000 Kauai Caucasian residents, standardized to the 1980 U.S. white population, was 153 for men and 92 for women with a combined rate of 118. The average patient age was 66.4 years. The head and neck was the most common anatomic site, with the extremities second. Subsequent new squamous cell carcinoma occurred in 13.8% of patients. Only one patient (2%) developed a recurrence after treatment. Twenty-five patients (43%) had basal cell carcinoma simultaneously or at other earlier times. CONCLUSIONS: In Kauai the incidence rate of squamous cell carcinoma is the highest yet documented in the United States. No consistent trend in incidence rates was appreciated during this 5-year period.

Adult↗

Cutaneous squamous cell carcinoma of the lower limbs in Goiânia, Goiás, Brazil.

BACKGROUND: Cutaneous squamous cell carcinoma is a common malignant neoplasm that affects areas that are exposed to the sun in fair-skinned people. It occurs less frequently on the lower limbs where other etiological factors are involved. OBJECTIVE: To determine the epidemiological aspects of cutaneous squamous cell carcinoma of the lower limbs in Goiânia. METHODOLOGY: Forty-three cases of cutaneous squamous cell carcinoma of the lower limbs from the Cancer Registry of the Population Base of Goiás, for the period between 1995 and 1999, were included in the study. RESULTS: Among the cases of cutaneous squamous cell carcinoma registered in this 5-year interval, 43 (4.6%) represented cases affecting the lower limbs. Of these individuals, seven (16.3%) were male and 36 (83.7%) female (P < 0.001). Those in the age group of 60 years and above represented 90.7% of the cases (P < 0.001). None of the patients had metastasis. CONCLUSION: Cutaneous squamous cell carcinomas on the lower limbs are more frequently seen in women older than 60 years of age, and they rarely metastasize.

Age Factors↗

Double squamous cell carcinomas, verrucous type and poorly differentiated type, of the urinary bladder unassociated with bilharzial infection.

A case of a 66-year-old Japanese woman with two synchronous urinary bladder tumors, namely verrucous carcinoma and poorly differentiated squamous cell carcinoma, is described. Both tumors were accompanied by widespread squamous metaplasia in the background and unassociated with bilharzial infection. The poorly differentiated squamous cell carcinoma, having a satellite tumor in its proximity, was large and in an advanced stage. The verrucous carcinoma was small with minimal invasion to the muscularis propria. The boundary between both tumors was well defined, suggesting colliding growth appearance. Immunoexpression of cytokeratins of verrucous carcinoma was similar to that of squamous metaplasia, and significant differences between verrucous carcinoma and poorly differentiated squamous cell carcinoma were demonstrated in their immunoexpression of cytokeratins.

Aged↗

Esophageal carcinosarcoma with basaloid squamous carcinoma and rhabdomyosarcoma components with TP53 mutation.

Carcinosarcoma of the esophagus is a rare tumor with a distinct pathological entity having squamous cell carcinoma as the most described carcinomatous component. This paper reports the first case of carcinosarcoma of the esophagus that showed predominant basaloid squamous carcinoma component in addition to squamous cell carcinoma and poorly differentiated carcinoma and sarcoma component. A 64-year-old male patient consulted for dysphasia and chest pain was examined and found to have gastrointestinal fiber-endoscope and a polypoid growth in the lower third of the esophagus. Partial esophagectomy was performed and the excised tumor showed histological features of carcinosarcoma with heterogeneous carcinomatous components with dominance of basaloid squamous carcinoma and minority of squamous cell carcinoma, poorly differentiated carcinoma, and sarcomatous component, immunohistochemically proven to be rhabdomyosarcoma. Immunohistochemical study and TP53 mutation analysis was carried out to explain the histogenesis of this rare tumor. The distinct immunohistochemical profiles of the carcinomatous and sarcomatous components suggested the possibility of transition from a carcinomatous to a sarcomatous component. The similar TP53 mutation in the carcinomatous and sarcomatous component suggested each of these components had the same origin, that is, the tumor was monoclonal in origin.

Biomarkers, Tumor↗

CD109 expression in squamous cell carcinoma of the uterine cervix.

CD109 is a cell surface protein, a member of the alpha(2) macroglobulin/C3,C4,C5 family of thioester-containing proteins. The authors have recently reported that high expression of the CD109 gene was detected in approximately half of the examined lung and esophageal squamous cell carcinomas as well as in the testis, and that CD109 has the characteristics of a cancer-testis antigen. In the present study CD109 expression in cervical squamous cell carcinoma was compared with that in endometrial adenocarcinoma by reverse transcription polymerase chain reaction (RT-PCR). The result demonstrated that CD109 expression is significantly higher in cervical squamous cell carcinomas than in endometrial adenocarcinomas and normal cervix and endometrium. In contrast, when expression of RET finger protein (RFP) and bromodomain testis-specific (BRDT) genes, which are also known to be highly expressed in the testis, was examined, no significant difference in their expression levels was observed between squamous cell carcinomas and adenocarcinomas. These findings suggest that CD109 may become a molecular target for the development of new therapeutics for squamous cell carcinoma of various tissue origins.

Adenocarcinoma↗

Primary bone carcinosarcoma: chondrosarcoma and squamous cell carcinoma with keratin pearl formation.

Malignant bone tumors with epithelial differentiation are extremely rare. Only one case of primary malignant bone tumor with distinct squamous cell carcinoma and chondrosarcoma has ever been reported. Reported herein is a case of primary malignant bone tumor with distinct squamous cell carcinoma and chondrosarcoma, so-called carcinosarcoma of bone, arising in the femur of a 53-year-old man. The tumor was located within the femur and was diagnosed by curettage as a well-differentiated chondrosarcoma. No primary tumor was detected in any other organ. Within a few months the tumor had rapidly grown toward the soft tissue, and hemipelvectomy was performed. Examination of the surgical specimen revealed that the tumor was mainly composed of undifferentiated spindle sarcoma cells with scattered foci of chondrosarcoma and of squamous cell carcinoma with keratin pearl formation. The patient died approximately 6 months postoperatively. At autopsy multiple metastases were detected in the heart, both lungs, muscles, and lymph nodes. Interestingly, the chondrosarcoma and squamous cell carcinoma components were observed in several metastatic foci. The tumors in both the previously reported case and the present case contained components of chondrosarcoma and squamous cell carcinoma with keratin pearl formation, and this combination of histological features may be a unique characteristic of carcinosarcoma of bone.

Bone Neoplasms↗

Histologically unique case of combined small cell and squamous cell carcinoma in a polypoid bronchial tumor.

Presented herein is a case of combined small cell and squamous cell carcinoma in a polypoid bronchial tumor, showing a histologically unique progression, in a 76-year-old Japanese man. A bronchofiberscopic examination revealed that the bronchus (left B3) was occluded by the polypoid tumor. Biopsies were performed, and the pathological diagnosis was poorly differentiated squamous cell carcinoma. The patient consequently underwent a left upper lung lobectomy. The surgical specimen was described as a 24 x 8 x 8 mm soft tumor, emanating from the bronchial wall (left B3). Histologically, the tumor had two distinct components: (i) nearly the entire tumor was composed of atypical small round cells, with a high nuclear-cytoplasmic ratio, in the lamina propria, under the basement membrane; and (ii) the surface of the tumor was composed of poorly differentiated squamous cell carcinoma that had proliferated primarily above the basement membrane but there was also some proliferation, seen as island-like formations, below the basement membrane. The histological diagnosis was combined small cell and squamous cell carcinoma. It was suspected that poorly differentiated squamous cell carcinoma, generated in the bronchial epithelium, had caused small cell carcinoma resulting from neuroendocrine differentiation during its invasion into the lamina propria.

Aged↗

Primary adenoid squamous cell carcinoma of the oral cavity.

Adenoid squamous cell carcinoma (ASCC) is an uncommon but well-recognized variant of squamous cell carcinoma that was first described by Lever in 1947. ASCC has been reported to originate in the sun-exposed skin of the head and neck and in other sites. An additional case of ASCC is reported here. The patient was a 64-year-old Japanese woman who requested examination of a reddish lesion on the left floor of the mouth. The biopsy material was diagnosed as squamous cell carcinoma. Clinical examination showed a well-circumscribed, 20 x 10 mm-sized lesion, which was categorized as cT2cN0cm 0. Tumor resection was therefore performed. Histologically, most parts of the lesion were conventional squamous cell carcinoma in situ, but the invasive part consisted of ASCC with gland-like or reticular appearance. The latter part was negative for mucin staining. Immunohistochemically, this lesion was positive for pancytokeratin, high-molecular-weight keratin, cytokeratin (CK) 7/8, CK19, E-cadherin and p53, but negative for vimentin, CK20, and S-100 protein. The Ki-67 labeling index was 50.3% in the ASCC part and 34.5% in the carcinoma in situ part. These findings and a review of the literature indicate that a gland-like feature of ASCC is associated with the loss of cell adhesion in the center of the cancer nests, and it can be confirmed simply by mucin staining to be neither an adenosquamous carcinoma nor ductal involvement of conventional squamous cell carcinoma.

Cadherins↗

High prevalence of cervical squamous cell abnormalities among HIV-infected women with immunological AIDS-defining illnesses.

AIM: To assess the results of Pap smear at postpartum scheduled visit, especially the prevalence of squamous cell abnormalities including association with CD4(+) T-lymphocyte count (CD4(+) count) levels at delivery among HIV-infected women between the years 1996 and 2004. METHODS: As part of the research and implementation programs of short course antiretroviral regimens for the prevention of mother to child perinatal HIV transmission in HIV-infected pregnant women delivered at Siriraj hospital, CD4(+) count at delivery and Pap smear at postpartum were evaluated. RESULTS: Among 636 women, 13.3% had squamous cell abnormalities. Seventy-seven cases (90.6%) of squamous cell abnormalities were low grade squamous intraepithelial lesions. The prevalence of squamous epithelial cell abnormalities detected by Pap smear, was higher in women whose CD4(+) count at delivery was < 200 cells/microL than in women whose CD4(+) count at delivery was > or = 200 cells/microL, with a significant difference (21.2%vs 12.2%). CONCLUSIONS: All HIV-infected pregnant women should be evaluated for clinical and immunological status during the antepartum period. Pelvic examination and Pap smear should be considered as a part of this evaluation. They should receive comprehensive health-care services that continue after pregnancy, including postpartum gynecologic examination and Pap smear. Women with normal cervical cytological findings but low CD4(+) count should be offered an antenatal Pap smear and long-term follow-up including a 6-monthly Pap smear.

CD4 Lymphocyte Count↗

The clinicopathological significance of p21 and p53 expression in esophageal squamous cell carcinoma: an analysis of 153 patients.

OBJECTIVE: The p21 gene is thought to play a central role in tumor suppression. The aim of this study was to examine the clinicopathological role of p21 and p53 in esophageal squamous cell carcinomas. METHODS: The expression of p21 and p53 proteins in 153 Chinese patients (131 men, 22 women) with resected esophageal squamous cell carcinomas was investigated by the immunohistochemical method. Correlation between p21 and p53 expression and clinicopathological features was examined. RESULTS: The expression of p21 and p53 was detected in 70% and 64% of the tumors, respectively. The staining of p21 and p53 was also found in squamous carcinoma in situ, dysplasia, and nontumor epithelium. p21 expression was often weak in the suprabasal cells and found in better differentiated tumors. There was no significant correlation between the expression of p21 and the abnormal accumulation of p53. The prognosis of the patients depended on the size, stage, and p21 expression of the lesion. In stage III lesions with tumor diameter < or = 7.5 cm (n = 93), patients with loss of p21 expression had better survival. The survival rates of patients were worse if they had expression of both p21 and p53. CONCLUSIONS: Thus, p21 and p53 had prognostic value for esophageal squamous cell carcinomas. Loss of p21 expression was shown without p53 alternations, indicating that other mechanisms are also involved in turning off the gene. The pattern of p21 and p53 expression predicts an aggressive clinical course of esophageal squamous cell carcinomas.

Actuarial Analysis↗

Differences in sialyl-Tn antigen expression between keratoacanthomas and cutaneous squamous cell carcinomas.

Keratoacanthoma and squamous cell carcinoma are common skin tumors, especially in immunosuppressed transplant recipients, but the distinction between these two types of epidermal neoplasia may be difficult. Sialyl-Tn (Sia-GalNAc-O-Ser/Thr) is a cell surface carbohydrate associated with hyperplasia in squamous epithelium, and correlated with poor prognosis in several human adenocarcinomas. Twenty-seven keratoacanthomas and 29 cutaneous squamous cell carcinomas were examined for the expression of sialyl-Tn and of the Ki67 epitope, the latter a marker for cell proliferation. By immunohistochemistry, basaloid tumor cells at the periphery of tumor nests showed some degree of sialyl-Tn expression in 16 keratoacanthomas (59%), while only three squamous cell carcinomas (10%) showed sialyl-Tn-positive basaloid tumor cells (p<0.001). Keratinized, differentiated tumor cells were more often sialyl-Tn-positive in keratoacanthomas (89%) than in squamous cell carcinomas (31%) (p<0.001). A striking sialyl-Tn-positivity in the basal cell layer was found in a border zone directly adjacent to most tumors of both types (88 and 88%). By immunohistochemical examination of parallel sections and by double immunofluorescence, sialyl-Tn antigen expression was primarily seen in cells that did not express Ki67, although some overlap was present. Keratoacanthomas from transplant recipients did not differ in sialyl-Tn expression compared to those from non-immunosuppressed patients. The results indicate that sialyl-Tn expression is not directly related to cell proliferation, but rather to cellular features of post-mitotic cells, and that sialyl-Tn is not associated with a malignant phenotype. Sialyl-Tn may be linked to tumor regression, as seen in keratoacanthomas.

Antigens, Tumor-Associated, Carbohydrate↗

Distribution and synthesis of type VII collagen in oral squamous cell carcinoma.

The distribution of the basement membrane anchoring fibril component type VII collagen was studied in oral squamous cell carcinoma by using in situ hybridization and immunohistochemical methods. The expression of type VII collagen in oral normal mucosa, lichen planus and epithelial dysplasias was also investigated. In squamous cell carcinomas, the signals for type VII collagen mRNA were located exclusively in malignant peripheral cells in tumour islands and in fibroblast-like cells among the stromal tissue. In normal buccal mucosa, type VII collagen mRNA expression was located in basal epithelial cells. In oral lichen planus and epithelial dysplasias, the signals for type VII collagen mRNA were also located in basal keratinocytes; however, the signal was especially strong in some epithelial cells. In oral squamous cell carcinomas, the linear immunohistochemical staining pattern of type VII collagen was noted surrounding partly squamous epithelial tumour cell islands, and a large number of tumour cells showed a cytoplasmic staining reaction using the type VII collagen antibody. Some fibroblast-like stromal cells also showed a positive immunostaining reaction. In conclusion, the results of this study indicate that a high synthesis level, but an impaired distribution of type VII collagen, are highly characteristic of squamous epithelial tumour cells.

Basement Membrane↗

Fine needle aspiration cytology as a diagnostic test for oral squamous cell carcinoma.

OBJECTIVE: The purpose of this study was to determine the possibility of using fine needle aspiration cytology (FNAC) as a primary diagnostic test in oral leukoplakia and squamous cell carcinoma. MATERIALS AND METHODS: The sample consisted of 12 cases of oral leukoplakia and 60 cases of oral squamous cell carcinoma. FNAC and biopsy was done on all cases. A cytological and histopathological correlation was undertaken to determine the proportion of cancers that can be accurately diagnosed by FNAC and its ability to identify differentiation gradings of squamous cell carcinomas. A blind examination was undertaken. RESULTS: In oral leukoplakias equal rates of true positive and false negative results were obtained. The overall positive correlation accounted for 33.33% with 33.33% inadequate FNACs. In oral squamous cell carcinomas 92.85% of true positive and 7.14% of false negative results were obtained. The differentiation gradings correlated in only 41.07%. The overall positive correlation was 86.66% with 6.66% inadequate FNACs. CONCLUSIONS: The present study indicates that FNAC can be used as a reliable diagnostic test for oral squamous cell carcinoma but its use in oral leukoplakia is of limited value.

Adult↗

The epidemiology of squamous cell carcinoma of the perineal region of sheep: abattoir and flock studies.

The roles of age, tail length and the Mules operation in the epidemiology of squamous cell carcinoma in ewes were studied. The prevalence of the disease in adult sheep slaughtered at 2 abattoirs was 0.08%. No cases occurred in lambs. Of all adult sheep condemnations before slaughter, 38.5% were due to squamous cell carcinoma. Of these sheep, 73.3% had a single lesion of the vulva (62.9%), tail (6.6%), or anus (3.8%), while 26.7% had lesions at more than one site. The number of lesions was significantly greater (p less than 0.01) in sheep with a radical Mules operation than in those with a modified Mules operation or not mulesed. Tails were significantly shorter (p less than 0.01) in affected than unaffected sheep. Small keratinised outgrowths on the skin of the tail and perineum were considered on histological grounds to be precursors of squamous cell carcinomas. On one affected farm 4% of ewes were culled in one year for gross lesions of squamous cell carcinomas. A further 3.5% of sheep with gross lesions and 25.3% with precursor lesions remained in the flock, undetected by the farmer. Gross lesions were not observed in ewes under 3 years of age, whereas precursors occurred in all age groups, including one-year-old ewes. The prevalence of lesions increased with age, from 0.43% in 5-year-old ewes to 5.14% in 6-year-old and 41% in 7-year-old ewes. Discriminant analysis indicated that age of ewe, tail length and the width of the healed Mules operation were important determinants of squamous cell carcinoma.(ABSTRACT TRUNCATED AT 250 WORDS)

Abattoirs↗

Intraepithelial and invasive squamous cell carcinoma of the conjunctiva: analysis of 60 cases.

AIM: To evaluate the clinical features, treatment results, and recurrence rates in patients with either intraepithelial or invasive squamous cell carcinoma of the conjunctiva. METHODS: Retrospective analysis of 60 cases (22 conjunctival intraepithelial and 38 invasive squamous cell carcinomas) to determine patterns of clinical presentation, aetiological factors, and treatment results. The mean patient age was 64 years old. 70% of the patients were male. Patients were treated with a variety of therapies, depending on the degree of tumour involvement; most cases were treated with frozen section controlled excision and adjunctive cryotherapy. Modified eye wall resection or enucleation was done for intraocular invasion and exenteration was done for orbital involvement. RESULTS: Red eye (68%) and ocular irritation (57%) were the most common presenting symptoms. 44% of the patients had other eye findings consistent with extensive solar exposure. 20% of the patients had a history of malignant skin tumours. Visceral malignancies developed in 8%. Scleral involvement was present in 14 (37%), intraocular involvement in five (13%), and orbital invasion in four (11%) cases with invasive squamous cell carcinoma. After a mean follow up of 56 months (18-226 months) the rate of new or recurrent tumours was 4.5% for intraepithelial squamous carcinoma and 5.3% for invasive squamous cell carcinoma. No patient developed metastases or tumour related deaths. CONCLUSION: Excision with intraoperative control of the surgical margins and adjunctive cryotherapy results in good tumour control rates.

Adult↗

Cytokeratin 14 as a marker of squamous differentiation in transitional cell carcinomas.

The presence of squamous differentiation in transitional cell carcinomas has been variably related to prognosis and response to radiotherapy. This study sought to establish whether cytokeratin (CK) 14, normally expressed in the basal cells of squamous epithelium, could be used as a reliable marker of the emergence of a squamous phenotype in transitional cell carcinomas. In a series of 42 tumours, CK14 was expressed in areas of squamous morphology, whereas CK20 identified continuing urothelial differentiation. Furthermore, focal positivity for CK14 was present in a proportion of tumours with no morphological evidence of squamous differentiation, suggesting that it is a more sensitive marker of phenotypic switch. Investigation of CK subtypes may be more powerful than morphology alone in clinical studies of transitional cell carcinomas as CK expression profiles have been related to treatment response in other tumour types.

Biomarkers, Tumor↗

Molecular analysis of ras oncogenes in CIN III and in stage I and II invasive squamous cell carcinoma of the uterine cervix.

AIM: To examine the prevalence of genital type human papilloma virus (HPV) and mutations at codons 12, 13, and 61 in H, Ki, and N-ras in CIN III and early invasive squamous cell carcinomas of the cervix. METHODS: Prevalence of HPV was examined in 20 CIN III and 20 stage I and II cervical carcinomas, using non-isotopic in situ hybridisation (NISH) and solution phase polymerase chain reaction (PCR). In addition, mutations at codons 12, 13, and 61 were examined in H, Ki, and N-ras in these CIN III and early invasive squamous cell carcinomas, to assess the prevalence of ras gene point mutations and to define where in the pathobiology of squamous cell carcinoma such events occur. A non-isotopic PCR/RFLP assay was used to define these mutations. RESULTS: Of the 20 CIN IIIs examined, 19 contained HPV 16 DNA sequences by PCR and NISH. Dual infection was not uncovered. The 20 early (stage I and II) invasive squamous cell carcinomas showed predominant HPV 16 positivity (17/20), with one case HPV 18 positive, confirmed on PCR and NISH. Activating mutations were not identified in any of the CIN III cases. Only one stage I, HPV 16 positive carcinoma showed an activating mutation in H-ras codon 12, which was not present in adjacent normal ectocervical mucosa from the same patient. CONCLUSIONS: ras Activation does not appear to occur in conjunction with HPV infection, particularly of HPV 16 infected high grade cervical intraepithelial neoplasia, or to occur commonly in early cervical squamous cell carcinoma. The postulated model of HPV linked carcinogenesis suggests malfunctional control of viral transcription as a necessary component of neoplastic progression. It is also clear that host gene alterations are equally necessary for HPV linked carcinogenesis to occur.

Carcinoma, Squamous Cell↗