Squamous Cell Component Research Articles

Adenosquamous carcinoma of the head and neck: criteria for diagnosis in a study of 12 cases.

Adenosquamous carcinoma (ASC) of the head and neck is an unusual neoplasm in which a general consensus with regard to diagnostic criteria has not yet been reached. In this study we report the clinicopathological results of 12 ASCs, with special attention to their histological and immunohistochemical characteristics in order to define this neoplasm more precisely. All the patients were male with a peak incidence in the sixth decade of life. The tumours were located most frequently in the larynx and oral cavity, followed by the nasal cavity and pharynx. ASCs had two distinct histological components. The most extensive one was an usual keratinizing squamous cell carcinoma, arising from the surface epithelium, where characteristically severe dysplasia or carcinoma in situ was found in all cases. The second component was an adenocarcinoma, usually displayed in the deepest areas of the tumour. Evidence of origin from salivary or seromucinous glands was not found. Immunohistochemical studies demonstrated in most cases positivity of glandular differentiated areas for carcinoembryonic antigen (CEA) (11/12), CK7 (9/12) and CAM5.2 (7/12), whereas the squamous cell component was unreactive or reacted only focally for these markers. High-molecular-weight cytokeratin 34BE12 was positive in both components and CK20 was always negative. All cases showed high expression of Ki67 antigen. Most of them had overexpression of p53 (8/12) and DNA aneuploidy (10/12). Fifty percent of patients with ASC died of disease after a mean period of 23 months (range 12-35 months). ASC of the head and neck is an aggressive neoplasm that originates in the surface epithelium of the upper respiratory tract. Severe dysplasia or carcinoma in situ is usually found and its recognition helps to make the diagnosis. In addition to mucin stains, positive immunoreactivity for CEA, CK7 and CAM5.2 helps to identify the glandular component.

Diagnostic and Pathogenetic Implications of Colorectal Carcinomas with Multidirectional Differentiation: A Report of 4 Cases

Multidirectional differentiation in colorectal carcinomas is a rare phenomenon. Four cases are reported herein, and their clinical and pathologic characteristics are discussed. Two men and 2 women between the ages of 56 and 76 years who presented with abdominal symptoms are included in this report. Two tumors were located in the right colon, one in the splenic flexure, and one in the descending colon. Distant metastases were evident at presentation in 3 of 4 cases. Histologically, two tumors exhibited neuroendocrine and glandular differentiation; the third tumor was an adenocarcinoma with a sarcomatous component and the fourth tumor showed 3 lines of differentiation (glandular, squamous, and sarcomatoid). In all tumors evaluated, areas of adenocarcinomas were positive for low-molecular weight cytokeratin (CAM 5.2) and mucicarmine, but negative for high-molecular weight cytokeratin (AE3). The squamous cell component was AE3 positive and CAM 5.2 negative. The neuroendocrine component was highlighted by neuroendocrine markers and the sarcomatoid component revealed smooth muscle differentiation. All tumors (except one mucinous tumor) were negative for cytokeratin-20 staining. One patient was on supportive care for terminal metastatic carcinoma, and 2 patients were being treated with adjuvant chemotherapy at the time of this report. Colon carcinoma with multidirectional differentiation is a rare event and may originate from stem cells within the gastrointestinal mucosa, and/or represent the convergence of multiple tumors arising at the same site. This type of tumor should be considered in the differential diagnosis of a bowel biopsy with multiple histopathologic variants.

Clonal analysis of adenosquamous carcinoma of the lung.

Adenosquamous carcinoma of the lung is a subset of pulmonary carcinomas, and comprises less than 4% of lung carcinomas. Its histogenesis remains unclear. The clonality of adenosquamous carcinoma from four female patients was analyzed to determine whether the clonality between the squamous cell and adenocarcinomatous components coincides. Each lesion was precisely microdissected from methanol‐fixed sections. Adjacent normal lung tissue was collected as a normal control. DNA was extracted for clonal analysis based on an X‐chromosome‐linked polymorphic marker, the human androgen receptor gene (HUMARA). HUMARA was found to be amplified with or without previous digestion by the methylation‐sensitive restriction endonuclease HpaII. All four cases were informative. Squamous cell and adenocarcinomatous components showed identical monoclonal patterns in all four patients. In one case, only the squamous cell carcinomatous component showed loss of heterozygosity of the HUMARA locus. The results suggest that the squamous cell and adenocarcinomatous components originate from the same cell.

Human papillomavirus DNA in adenosquamous carcinoma of the lung.

AIM: To investigate the presence of human papillomavirus (HPV) DNA in adenosquamous carcinoma of the lung--which is relatively common in Okinawa but not in mainland Japan--and examine its histological features....

Metaplastic carcinomas of the breast—fine needle aspiration (FNA) cytology findings

Metaplastic carcinomas of the breast are defined by mesenchymal and/or squamous cell components associated with ductal carcinoma and may raise diagnostic problems in FNA cytology. We reviewed FNA smears of a series of nine cases; seven were compared with histological sections and two with cell-block sections. The cytological pattern was diagnostic of carcinoma in six cases; in two cases a diagnosis of sarcoma/phyllodes tumour was considered, as cells were predominantly spindle-shaped. One case had a pleomorphic adenoma type pattern. The cytological findings suggesting a diagnosis of metaplastic carcinoma include a liquid aspirate, a proteinaceous or chondromyxoid background and a poorly differentiated tumour with multinucleated giant cells, neoplastic or histiocytic. A definite diagnosis requires the presence of both carcinomatous and metaplastic (squamous/mesenchymal) components.

Effectiveness of automated cervical cytology rescreening using the AutoPap 300 QC System.

This study assesses the performance of the AutoPap 300 QC System in identifying false-negative (FN) smears in a slide population previously screened as normal and compares the detection rate to that achieved with a random rescreen of the same slide population. A total of 1,840 "normal" smears were rescreened both manually and by the AutoPap 300 QC System. Overall, a total of 7 FN slides were detected. At QC selection rates of 30% and 20% the device achieved sensitivities for detection of FN smears of 57.19% (4/7) and 42.8% (3/7), respectively. This represents a three- to fourfold enrichment in the number of FN smears over that obtained by a random rescreen of a similar proportion of cases. None of the FN slides were identified by either method at a 10% rescreening rate. The ability of the device to detect slides previously classified as abnormal (n = 139) and FN (n = 40) was also studied. The overall sensitivity to abnormal smears at QC selection rates of 10%, 20%, and 50% was 61.9%, 77.0%, and 94.2%, respectively. Improved sensitivity to smears classified as LSIL or worse (n = 112) was obtained for corresponding selection rates (61.6%, 75.9%, and 93.8%). Sensitivity to FN slides classified as LSIL or worse (n = 17) for QC selection rates of 10%, 20%, and 50% was 29.4%, 70.6%, and 88.2%, respectively. The sensitivity and specificity of the device to an adequate squamous and endocervical cell component was also determined. At predetermined thresholds, the overall sensitivity to slides with an inadequate squamous cell component (n = 55) and to those smears with an endocervical cell component (n = 1.587) was 81.8%, and 82.7% respectively. The study demonstrated that the AutoPap 300 QC System is superior to human random rescreen for the identification of FN smears although only a marginal improvement was noted due to the small sample. Further studies are required using a larger number of smears to fully assess the value of the device in quality control mode. The device also has the potential to improve the accuracy of specimen adequacy determinations and to serve as a useful adjunct to existing quality control measures designed to monitor individual performance and reporting accuracy.

SQUAMOUS CELL CARCINOMA OF THE BREAST-REPORT OF A CASE-

A case of squamous cell carcinoma of the breast, which is regarded as squamous metaplasia with adenocarcinoma, is reported. A 42-year-old woman was seen at the hospital because of a tumor of the left breast and pain. Mammography and echography revealed a breast cancer. Modified radical mastectomy was carried out. Histologically, the tumor was squamous cell carcinoma and axillary lymph node involved squamous cell carcinoma mixing with adenocarcinoma cells. There was recurrence on the left breast skin one year after the operation. The skin biopsy was carried out. Histological examination revealed that the lesion was predominaly comprised of sold-tubular carcinoma cells, with scarce squamous cell components.

Relationship between epidermal growth factor receptor (EGF-R) and various prognostic factors in human endometrial carcinoma.

Eighty primary endometrial carcinomas were analyzed for the presence of epidermal growth factor receptors (EGF-R) by the use of a single point (1ng 125I-EGF) EGF-R assay. Fifty percent of the analyzed specimens were EGF-R positive (EGF-R(+)) with binding capacities > 1 fmol mg-1 and 15% bound > 7 fmol mg-1. The EGF-R status was correlated with different clinically relevant prognostic factors and the survival rates were analyzed. The correlations revealed no significant differences in the grade of tumor differentiation and in the depth of myometrial invasion. The advanced tumor stages III and IV and tumors with a squamous cell component in the histologic examination expressed EGF-R in a higher percentage. Between the EGF-R and the steroid receptor status existed a weak negative correlation. Estrogen receptor positive tumors were in 47% and progesterone receptor positive tumors in 45% EGF-R (+). The corresponding number for the receptor negative tumors were 57 and 65%. Life table analyses were performed with different cut-off limits for specific EGF binding ranging from > 1, > 3, > 5 and > 7 fmol mg-1. Dependent on the cut-off limits the analysis demonstrates a reduced survival probability for patients with EGF-R+ tumors. These differences were mainly found in the small group with a high number of EGF-R's (> 7 fmol). The analysis of tissue extracts for the presence of factors binding to the EGF-R revealed in some specimens high concentrations of EGF-like factors. By the use of TGFa (transforming growth factor alpha) immunohistochemistry we were able to demonstrate that the tumor cells produce TGFa, whereas the stroma is TGFa negative. We assume that the EGF-like factors consist mainly of TGFa.

Signet-ring cells in squamous cell carcinoma of the cervix and in non-neoplastic ectocervical epithelium.

Two cases of cervical carcinoma and two cases of normal ectocervical epithelium with a squamous signet-ring cell component are presented. In one carcinoma the vacuolization was so prominent that it partially obliterated the epithelial pattern of the tumor. Paraffin specimens were studied with a panel of histo- and immunohistochemical stains and by electron microscopy. The vacuoles of the squamous signet-ring cells did not contain glycogen, mucopolysaccharides or masses of intermediate filaments. The findings are discussed in relation to possible human papillomavirus and Chlamydia trachomatis infection. The true nature and possible clinicopathologic implications of the squamous carcinoma with signet-ring cells remain to be established, but the phenomenon may cause diagnostic difficulties, especially in biopsy specimens.

Adenosquamous Carcinoma of the Pancreas

We report a case of a primary pancreatic adenosquamous carcinoma, an unusual malignancy that displays angiographic and computed tomography (CT) features atypical of primary pancreatic adenocarcinoma. The tumor consisted almost entirely of squamous cell components. The giant tumor stain and new vessel formation seen with angiography and the significant enhancement of the tumor on CT scan were considered to be characteristic of squamous cell carcinoma of the pancreas. The tumor we report grew expansively, mainly ventrally and barely in the dorsal direction, leaving major arteries and veins almost intact. A ⁶⁷Ga scan showed a high accumulation at the site of the tumor. The combined use of angiography, CT scan, scintigraphy and other radiographic methods is very helpful in the diagnosis of squamous cell carcinoma and adenosquamous carcinoma, which are very difficult to distinguish from adenocarcinoma on clinical presentation.

THREE CASES OF ADENOSQUAMOUS CARCINOMA OF THE EXTRAHEPATIC BILE TRACT

Adenosquamous carcinoma, a mixed type of adenocarcinoma and squamous cell carcinoma, is a relatively rare tumor in the bile duct and papilla of Vater. Three cases of adenosquamous carcinoma were examined from among 35 cases of bile duct cancer and 10 cases of carcinoma of the papilla of Vater who underwent operation in our hospital during the last 20 years. The first case was a 41-year-old woman who suffered from adenosquamous carcinoma of the papilla of Vater. She died from local recurrence 9 months after surgery. The second case was a 50-year-old woman who suffered from adenosquamous carcinoma of the inferior part of the bile duct. She died 3 years and 1 month after surgery with bone metastasis. The third case was a 71-year-old man who suffered from adenosquamous carcinoma of the middle part of the bile duct. He died 4 months after surgery due to liver metastasis.Microscopic examination revealed the mixed type of well-differentiated adenocarcinoma and squamous cell carcinoma with a transitional zone, suggesting these adenosquamous carcinomas originated from adenocarcinoma cells through squamatization. All three cases, in spite of having undergone pancreatoduodenectomy, had poor prognoses compared with other cases of bile duct cancer of the same part, indicating that the appearance of a squamous cell component is one of the factors leading to poor prognosis.

Relationship between structure and T-lymphocyte maturation in human thymomas. Enzyme histochemical and immunohistological studies.

Twenty-six human thymomas were studied in an attempt to correlate their morphological appearance with the type and degree of T-lymphocyte maturation, as determined by acid alpha-naphthyl-acetate esterase (ANAE) activity and immunological analysis. Four normal human thymuses were used for purposes of comparison. Two morphological patterns were identified in the thymomas. The distinction was based largely on similarities between the neoplastic epithelial cells and normal cortical and medullary epithelial cells, and on the relative proportions of epithelial cells and lymphocytes. By these criteria "medullary" and "cortical" patterns were identified. In several thymomas both patterns were present in the same tumor ("mixed-type pattern"), producing alternating dark cortical-like areas and lighter foci of medullary differentiation. A good correlation was found between the two patterns and the phenotype of the T-associated lymphoid component. ANAE activity, which was completely lacking in normal cortical thymocytes, was almost absent in the phenotypically immature T-cells of cortical-type thymomas. By contrast, in the medullary-type thymomas, T-cells showed immunological features in common with medullary thymocytes. This was characterized by strong ANAE activity in the majority of cells with a staining pattern corresponding to that of peripheral T-lymphocytes. In addition, most of the proliferating epithelial cells in medullary-type thymomas stained strongly with anti-cytokeratin and anti-epidermal-type keratin antisera. In the mixed-type thymomas the epithelial cell morphology and the immunohistochemical and enzymic features of the T-cells were found to be closely related to the respective cortical--or medullary-like areas. It was concluded that the various characteristics of normal thymic cortex and medulla studied are also present in thymomas. In particular, in medullar-type thymomas the presence of many of the features of normal thymic medulla, such as a squamous cell component, macrophages and interdigitating reticulum cells, may constitute a microenvironment which operates actively in T-cell education. This may account for the functional activities, characteristic of peripheral T-lymphocytes, which T-lymphocytes attain in these thymomas.

Establishment and characterization of two human ovarian endometrioid carcinoma cell lines (with or without squamous cell component)

The cell lines designated HMOA and HNOA were established from human ovarian adenoacanthoma and from a mouse graft of human ovarian endometrioid adenocarcinoma, respectively. These cell lines grew well without interruption for over 20 months. The cultured cells of both HMOA and HNOA lines were spindle, polygonal, and columnar, and showed a jigsaw puzzle-like arrangement and a piling-up tendency devoid of contact inhibition. When the HMOA cells were maintained at the confluent stage, the cells formed cysts and/or squamous metaplasia. The chromosome number of both cell lines varied widely and showed aneuploidy, while the modal chromosome number was stable at the diploid range. Both of these cell lines, HMOA and HNOA, were transplanted into the subcutis of BALB/c nude mice and produced well-differentiated adenoacanthoma and poorly differentiated endometrioid adenocarcinoma, respectively. HMOA cells were characterized as producing large amounts of CA125 (ovarian carcinoma marker), in vitro, in the cyst-forming phase. The HNOA cells, however, did not produce CA125.

Primary multipotential malignant neoplasm of bone: Chondrosarcoma associated with squamous cell carcinoma

A primary neoplasm of the proximal humerus in a 68-year-old woman was unique histologically in that it contained both malignant cartilaginous and squamous cell components. The epithelial differentiation was confirmed by the demonstration of keratin by immunohistochemical techniques and of basement membrane, tonofilaments, and well-formed desmosomes by electron microscopy. The patient died 3 1/2 years after the onset of symptoms, without clinical evidence of either a primary tumor elsewhere or metastasis. The differential diagnosis from other bone tumors with epithelial differentiation, such as adamantinoma and "primitive multipotential primary sarcoma," is discussed. This is a rare primary neoplasm of bone of unknown histogenesis. Intermutability or metaplasia between mesenchymal and epithelial tissues is a possibility. The tumor probably originated from multipotential stem cells with the ability to undergo biphasic or dual differentiation toward mesenchymal and epithelial elements.

Carcinoma of the anal sac glands in ranch mink.

During a 14-year period, carcinoma of the anal sac apocrine glands was found in 52 pastel and 8 sapphire mink (Mustela vison) kept for studies on slow viral diseases. The pastel mink varied in age from 72 to 135 months (mean age 108 months), the sapphire mink from 63 to 100 months (mean age 81 months). All but one pastel mink were females. The primary tumor varied in size from masses that caused bulges in the perineum to those that were found only after microscopic examination of the anal sac glands. Although the primary tumor grew mainly by expansion with little local infiltration, 41 of the 60 tumors had metastasized to the regional lymph nodes and sometimes also to more distant sites. The striking propensity of the carcinoma to metastasize while still small, even microscopic, often resulted in massive secondary growths, notably in the iliac lymph nodes. Hypercalcemia did not accompany the carcinoma. Its varied microscopic appearance included solid, glandular, squamous cell, and spindle or round cell components. Combinations of them formed mixed or complex histologic patterns, no doubt largely attributable to neoplastic proliferation of myoepithelial cells and squamous metaplasia of the apocrine gland epithelium. Although its cause remains obscure, the carcinoma appeared to arise from small foci of hyperplastic apocrine glands, sometimes in relation to both anal sacs. The tumor is a common and distinctive expression of neoplasia in older ranch mink.

Unstable Cellular Differentiation in Adenosquamous Cell Carcinoma<xref ref-type="fn" rid="FN2">2</xref><xref ref-type="fn" rid="FN3">3</xref>

For the determination of whether two or more stem lines with fixed of stable differentiation are present in a growing mixed adenosquamous cell carcinoma, two different mixed tumors, derived from transformed F344 rat tracheal epithelium, were dissociated and ten single cells were isolated from each tumor. Each of these single cells was allowed to grow 27 population doublings to form a clonal population. All clones were then inoculated into animals for the assessment of in vivo differentiation. All cell inocula produced carcinomas within 7-70 days. Of the ten single cell clones isolated from the first tumor, seven clones produced mixed adenosquamous carcinomas and three produced adenocarcinomas in which no squamous cell component was found. From the second tumor, eight clones produced mixed tumors and two produced squamous cell carcinomas in which no adenocarcinoma component was found. The mixed tumors derived form clones contained widely varying proportions of adeno and squamous components. Recloning of the cloned lines yielded populations that produced mixed adenosquamous cell carcinomas upon inoculation in vivo. Comparison of tumor phenotypes from clones of early and late passages further confirmed the instability of differentiation in these neoplastic epithelial cells. These studies strongly suggest that the mixture of differentiated cell types in adenosquamous cell carcinomas is not the result of a mixture of stem cells with one fixed phenotype within the tumor, but rather is the result of an instability of differentiation; the neoplastic cells can express both types of differentiation.

Methylcholanthrene-induced endometrial carcinoma in mice and rats: a histological and ultrastructural study.

Endometrial carcinoma was induced with a high incidence in various strains of mice and rats, by means of intrauterine application of 3‐methylcholanthrene under continuous estrogen stimulation. And a transplantation study of one of induced adenoacanthomas in A strain mice was successfully carried out.The endometrium in the early stage of the experiment showed atypical adenomatous hyperplasia that was soon followed by atypical adenomyosis. In the group of ICR mice treated with 0.8 mg of MCA, carcinomatous change was seen in atypical glands of the endometrium after the 14th week of the experiment. Carcinoma invasion and metastasis to visceral organs were found after 19 weeks.The majority of induced carcinomas of the endometrium were histo‐logically classified as either adenocarcinoma or adenoacanthoma, and only a few were regarded as squamous cell carcinoma. Ultrastructural study demonstrated that the cells in adenocarcinoma reveal poor cellular differentiation, while in adenoacanthoma the cells show better functional differentiation. The squamous cell component in adenoacanthoma is produced by squamous metaplasia of carcinoma cells.All induced sarcomas of the uterus were of myometrial smooth muscle cell origin, many of which, were accompanied by endometrial adenocarcinoma to be resulted in a form of carcinosarcoma.In an ICR mouse, sacrificed before uterine tumefaction, many extra‐as well as intracellular fine particles consistent with C‐type tumor viruses were detected in the myometrium.

Basal Cell Carcinoma of the Vulva

The incidence of basal cell carcinoma of the vulva is 2% to 3% of all vulvar malignancies. It occurs most commonly in patients over 60 years old. Leukoplakia is not a predisposing factor. Treatment of choice is wide local excision although some authors recommend a regional node dissection if any squamous cell component is present. The use of curettage followed by electrodesiccation is briefly discussed.