Oesophageal basaloid squamous cell carcinoma: a unique clinicopathological entity with telomerase activity as a prognostic indicator.

Oesophageal basaloid squamous cell carcinoma (BSCC) is uncommon and has been reported to have a worse prognosis than squamous cell carcinomas (SCCs), but this tumour has not been fully characterized. The aim of the present study was to analyse the clinicopathological features of a large cohort of patients with oesophageal BSCC treated at a single institution. The pathology of 756 primary oesophageal cancers treated between January 1989 and December 1998 was reviewed. Tumours that fulfilled the diagnostic criteria of BSCC were identified and were compared with SCC. Their expression of MIB-1, DNA ploidy, and telomerase activity were also studied. Thirty Chinese patients (25 men and five women) with BSCC were found, comprising 4% of patients with oesophageal cancer treated by surgical resection in the study period. Their median age was 67 years (range 40-78 years). Dysphagia was usually the main presenting symptom. Other concomitant malignant tumours were seen in three patients and paraneoplastic glomerulopathy in one. Five tumours were located in the upper third, 19 in the middle third, and six in the lower third. The median length was 5.8 cm (range 2-12 cm). The median MIB-1 score of BSCC was 750 (range 400-858) and was higher than that of SCC (p=0.003). The primary tumour and metastatic BSCC were aneuploid, as detected by flow cytometric analysis in nine patients. Telomerase activity was positive in 95% (19 out of 20) of the cases analysed. The 5-year survival of patients with BSCC was 12%. Distant metastases were seen in 53% (n=16); lung and liver were the most common sites. The median survival of patients with tumours which had a high level of telomerase activity was significantly shorter than those with low levels of telomerase activity (1 vs. 27 months) (p=0.001). The median survival of patients with BSCC and SCC was 26 and 16 months, respectively (p=0.3). In conclusion, BSCC has distinctive clinicopathological features and its long-term prognosis is no worse than SCC. The level of telomerase activity may have a prognostic role.     

Atypical parakeratosis: A marker of dysplasia?

The Bethesda System categorizes atypical parakeratosis (APK) as “ASCUS or SIL depending on the degree of cellular abnormalities.” APK, however, is not well-defined. We retrospectively reviewed 68 cervicovaginal specimens with follow-up material to identify specific criteria and clinical significance of APK. APK cells were small cells, 2–3 times the diameter of a neutrophil, with dense, orangeophilic cytoplasm, high nuclear cytoplasmic ratio, dense, often uneven chromatin, and irregular nuclear contour. Of 62 cases with APK, 37 had accompanying dysplastic cells. Of 25 cases with APK alone, follow-up revealed 12 with squamous intraepithelial lesion (5 HSIL and 7 LSIL) and 13 with benign changes. A major diagnostic pitfall of APK was inflammation with degeneration. Abundant APK cells, minimal inflammation and degeneration, and previous history of dysplasia frequently were associated with follow-up SIL. The findings of this study identify APK as an important marker for dysplasia that warrants careful evaluation and follow-up. Diagn Cytopathol 1996;15:288–291. © Wiley-Liss, Inc.     

Abnormalities of differentiation and maturation in the oesophageal squamous epithelium of patients with tylosis: morphological features

Tylosis is an autosomal dominant inherited defect of keratinization, associated in two Liverpool families with a high risk of developing oesophageal squamous carcinoma. In 29 individuals, followed by regular endoscopy and biopsy, we have noted several morphological abnormalities of the epithelium in this pre-cancerous condition. A control group of 43 non-tylotic patients with normal oesophageal histology and a further 26 patients with acute oesophagitis was used for comparison. Recognizable dysplasia was confined to the older age range in the tylotic group and was present in four patients. Almost half of the patients showed acute inflammation. Abnormalities of maturation were common, the most frequent being the presence of prominent basophilic inclusions and clear cell acanthosis, with parakeratosis and frank surface keratinization present in smaller numbers. There was, however, no statistically significant difference between the tylotic and inflamed control groups for any of these features. The only feature to show a significant difference between these groups was the presence of individual cell keratinization. The results suggest that in the oesophageal epithelium of the patients with tylosis, inflammation is the predominant abnormality, together with individual cell keratinization, and that these lesions appear in a much younger age group than dysplasia.     

Metallothionein expression in mobile tongue squamous cell carcinoma: associations with clinicopathological parameters and patient survival

Theocharis S, Klijanienko J, Giaginis C, Rodriguez J, Jouffroy T, Girod A, Point D, Tsourouflis G & Sastre‐Garau X
(2011) Histopathology 59 , 514–525 Metallothionein expression in mobile tongue squamous cell carcinoma: associations with clinicopathological parameters and patient survival Aims: Metallothionein (MT) has been implicated in several aspects of cancer pathobiology, such as differentiation, proliferation, apoptosis and invasion. The aim of the present study was to evaluate the clinical significance of MT expression in mobile tongue squamous cell carcinoma (SCC). Methods and results: MT protein expression was assessed immunohistochemically on 49 mobile tongue SCC specimens, and was analysed in relation to clinicopathological characteristics, and overall and disease‐free patient survival. All of the examined mobile tongue SCC cases showed MT positivity in tumour cells; however, neither MT overexpression nor staining intensity was significantly associated with clinicopathological parameters. MT cellular distribution was significantly associated with histopathological grade of differentiation and depth of invasion (P = 0.0188 and P = 0.0484, respectively). MT staining intensity was identified as a significant predictor of overall patient survival at both univariate (P = 0.0377) and multivariate (P = 0.0472) levels. Twenty‐seven (55.10%) of the examined SCC cases showed MT positivity in squamous tongue epithelium adjacent to the tumour, the MT positivity being correlated with depth of invasion (P = 0.0281), vascular invasion (P = 0.0194), and the existence of lymph node metastases (P = 0.0194). Conclusions: MT may be implicated in the development and progression of mobile tongue SCC and could be considered as a useful clinical marker for patient management and prognosis.     

Immunohistochemical staining patterns of keratins in normal oesophageal epithelium and carcinoma of the oesophagus

To clarify the keratin staining patterns of invasive carcinoma of the oesophagus, 22 cases of formalin-fixed paraffin-embedded surgical specimens were examined immunohistochemically with the labelled streptavidin biotin method using a panel of six different monoclonal anti-keratin antibodies. The antibody reacted adequately when antigen was retrieved in a microwave oven, and the relationship between morphological characteristics and keratin reaction patterns was analyzed in carcinomas and compared with adjacent histologically normal epithelium. In the normal oesophageal epithelium, AE3 and CK8.12 labelled all layer of cells, KS-1A3, E3 and KL1 labelled suprabasal cells, and LL002 selectively labelled the basal cells. In squamous cell carcinomas, AE3, CK8.12, KL1 and LL002 labelled almost all the tumour cells regardless of their differentiation, E3 only labelled keratinized cells, while marked decrease or loss of KS-1A3 staining was seen in all cases examined. Therefore, the characteristic profile of squamous cell carcinoma was a strong and diffuse expression of keratin 14 and 16, strong but localized expression of keratin 17, and loss of keratin 13 expression. Undifferentiated carcinoma totally lacked all keratin reactivity. The findings suggested that the neoplastic epithelial cells showed different keratin reactivity and distribution compared to normal oesophageal epithelium. In addition, histologically normal epithelium, dysplasia and carcinoma-in-situ adjacent to or overlying carcinoma expressed keratin 14.     

Barrett's dysplasia and the Vienna classification: reproducibility, prediction of progression and impact of consensus reporting and p53 immunohistochemistry

Aims:  The Vienna classification is used to classify dysplasia in Barrett's oesophagus (BO), but reproducibility and value of diagnosis of lower grades in particular are often questioned. The aim was to test the diagnostic variability and correlation with patient outcome and to attempt to define histological features causing discrepant diagnoses, as well as to test the impact of adding p53 immunohistochemistry on reproducibility and prediction of outcome.
Methods and results:  One hundred and forty-three patients with 154 sets of biopsy specimens originally diagnosed with Barrett's dysplasia were retrieved from the pathology records of Nottingham University Hospital. Thirty-two Barrett's patients without dysplasia were added. Anonymized slides were graded independently by five pathologists without and with p53-stained slides. Interobserver variation, correlation with outcome and diagnostic accuracy were determined. Weighted κ scores between pairs of pathologists showed substantial agreement and improved after p53 immunohistochemistry. Agreement with the original diagnosis was substantially lower. Fourteen of 34 low-grade dysplasias (LGD) and 27 of 30 high-grade dysplasias on consensus progressed within 10 years compared with 18/94 and 28/39 of original diagnoses. Progression correlated with p53 positivity.
Conclusion:  The Vienna classification is useful and reproducible in BO. Consensus diagnosis by gastrointestinal pathologists produces high specificity and predictive value, even for LGD. p53 immunohistochemistry assists in diagnosis in difficult cases and predicts progression.     

Cytologic correlates of benign versus dysplastic abnormal keratinization

The purpose of this study was to determine the cytologic and histologic features that differentiate benign from squamous intraepithelial lesion (SIL)-associated cervical abnormal keratinization, defined as hyperkeratosis, parakeratosis, or individual cell dyskeratosis. Fifty-four cervical Papanicoloau (Pap) smears that contained abnormally keratinized cells were reviewed without knowledge of the concurrent biopsy. Twenty-three Pap smears were diagnosed as SIL and the corresponding biopsy showed SIL in 21 (91%) of these cases. Of the 23 Pap smears diagnosed as negative for SIL, the corresponding biopsy in 20 cases (87%) showed benign (SIL negative) abnormal keratinization. Eight Pap smears showed squamous atypia, of these 5 showed SIL on biopsy, and the other 3 revealed benign keratinization. The Pap smear correlates of the 25 biopsies that were negative for SIL included marked hyperkeratosis (18/25–72 vs. 5/29–17% for biopsies with SIL) and regular nuclear membranes (16/18–89% cases with nucleated dyskeratotic cells vs. 5/29–17% for biopsies with SIL). The cytologic correlates of the 29 biopsies that showed SIL included irregular chromatin clumping (27/29–93% vs. 3/18–17% for biopsies without SIL), and a disorganized growth pattern (24/29–83 vs. 5/25–20% for biopsies without SIL). It is concluded that the cytologic distinction between benign and SIL-related Pap smears with abnormal keratinization can be reliably made by the degree of hyperkeratosis, nuclear chromaticity pattern and contour, and the growth pattern of the dyskeratotic cells. Diagn. Cytopathol. 1997;17:447–451. © 1997 Wiley-Liss, Inc.     

Carcinoma of the oesophagus with spindle cell features

There is considerable confusion surrounding the histogenesis and nomenclature of squamous cell carcinomas of the oesophagus with spindle cell elements. These tumours, many of which are polypoid, have been variously called carcinosarcoma, pseudosarcoma and polypoid carcinoma of the oesophagus. A study of three recent cases strongly supports the theory that these tumours are squamous cell carcinomas with spindle cell metaplasia. They are not necessarily polypoid and adenocarcinomatous elements may also be present.     

Carcinoma of the extrahepatic biliary tract: a clinicopathological and immunohistochemical study

The clinical and histological findings in 15 cases of carcinoma arising from the extrahepatic biliary tract are reviewed. The clinical findings are in agreement with previously reported series and the dismal prognosis is confirmed. The prognosis does not appear to be related to tumour size, site, mitotic count or laboratory data on presentation. Only histological grading of the tumour is related to prognosis. Perineural tumour infiltration was a prominent feature and dysplasia within adjacent bile duct epithelium was present in five cases. The value of carcinoembryonic antigen (CEA) as a histological tumour marker was investigated. All tumours from the upper and middle biliary tree expressed this antigen. Although immunocytochemistry is seldom needed to assess malignancy in large surgical resection specimens anti-CEA helps delineate the extent of tumour infiltration and discriminates between normal and dysplastic or malignant epithelium; anti-CEA may also be helpful in identifying foci of malignancy in small sclerotic biopsy specimens.     

A "new" autosomal dominant genodermatosis characterized by hyperpigmented spots and palmo- plantar hyperkeratosis

A previously undescribed genodermatosis consisting of tiny hyperpigmented spots aggregated in irregular maculae and mainly localized in the regions exposed to light is reported. Hyperkeratotic papules in the palms and soles were also present. Autosomal dominant inheritance is concluded.     

Variant of odontoonychodermal dysplasia?

In this case report we describe a patient with all the manifestations seen in the odontoonychodermal dysplasia syndrome, except for the shape of teeth and mild mental deficiency. © 1995 Wiley-Liss, Inc.     

A keratin K10 gene mutation in a Japanese patient with epidermolytic hyperkeratosis

Summary Epidermolytic hyperkeratosis (EHK), or bullous congenital ichthyosiform erythroderma, is characterized by generalized erythroderma, ichthyosiform skin and blistering, and is caused by an aberration of the keratin intermediate filaments. In this study, we examined keratin K10 and 1 gene mutations in a Japanese EHK patient who had severe ichthyosiform erythroderma at birth and developed subsequent blistering. The patient had a G to A transition at codon 156 of the keratin K10 gene, which resulted in an arginine (Arg)→histidine (His) substitution in the helix initiation peptide of the highly-conserved 1A domain in keratin K10. This is the first mutation report of a Japanese patient with EHK, although the position and mode of the mutation identified here did not differ from those in reported Western cases.     

Fatal hyperkeratosis syndrome in four siblings due to dolichol kinase deficiency

A diagnostic journey began in 1966 when a male was born with a lethal hyperkeratosis of undetermined etiology, only to be followed by three additional siblings with the same unknown disorder. All four siblings had unique circumferential skin constrictions on all of their digits. They died within 5 days after birth with no diagnosis or etiology established. The first author (BDH) maintained notes, partial medical records, photographs, and comments about one autopsy report. This information was regularly revisited in the hope of finding a literature match, but no etiological diagnosis was forthcoming. However, in 2017, Rush et al. reported two siblings with similar phenotype in whom they found dolichol kinase deficiency (DOLK). Ultimately, our family was relocated and DNA isolated from the pathology slides of the third affected infant showed compound heterozygous pathogenic variants in the DOLK gene. The variants were in trans, with different missense variants from the mother and father. This 52‐year diagnostic pursuit, culminated in an answer that gave the family an explanation for their losses.     

Spindle cell squamous carcinoma of the oesophagus: an analysis of 17 cases, with new immunohistochemical evidence for a clonal origin

AIMS: To study the morphological and immunohistochemical characteristics of spindle cell squamous carcinoma of the oesophagus, in order better to understand the histogenesis of this tumour. METHODS AND RESULTS: In this study we analysed the morphological and immunohistochemical characteristics of 17 cases of spindle cell squamous carcinoma of the oesophagus. Most tumours were polypoid, but tumours with an ulcerated and infiltrative pattern were also observed. Histologically, most tumours were of superficial type, with a characteristic morphological aspect consisting of two types of tumour cells, i.e. differentiated squamous cells, and spindle cells with transition zones between the two components. On immunohistochemistry, the squamous cells were positive for cytokeratin and the spindle cells showed variable expression of cytokeratin, vimentin and smooth muscle actin. p53 protein was over-expressed in 10 cases, both tumour cell types showing strong nuclear positivity. In most tumours, E-cadherin was expressed in the squamous cells and absent in the spindle cells. CONCLUSIONS: The similar pattern of p53 protein expression in the two tumour cell types of spindle cell squamous carcinoma of the oesophagus suggests their common origin. The change in adhesion molecule expression with loss of E-cadherin expression may be associated with the acquisition of spindle cell morphology by the squamous tumour cells.     

Superficial adenocarcinoma of the oesophagus arising in Barrett''s mucosa with dysplasia: a clinico-pathological study of 12 patients

Superficial adenocarcinoma of the oesophagus is defined as carcinoma limited to the mucosa or submucosa regardless of lymph node status. Columnar epithelium lined lower oesophagus, now generally referred to as Barrett's oesophagus, is probably the main cause of adenocarcinoma in the lower oesophagus. Twelve cases of superficial adenocarcinoma arising in Barrett's oesophagus are presented. They were observed over a 6 year period and taken from a series of 50 cases of patients with Barrett's oesophagus and adenocarcinoma, a prevalence of 24%. Endoscopic diagnosis of malignancy was made in six patients. The initial biopsies showed an adenocarcinoma in six patients and some degrees of dysplasia in the other six patients. Prior to surgery, a histological diagnosis of adenocarcinoma was made in all twelve patients. In four patients the adenocarcinoma was confined to the mucosa, and in eight it extended to the submucosa. One patient had a metastatic lymph node. Ten patients are alive without evidence of tumour spread after a mean follow-up of 30 months.     

The diagnosis of dysplasia and malignancy in Barrett's oesophagus

Barrett's metaplasia is associated with an increased risk for adenocarcinoma. Adenocarcinoma develops through a multistep process characterized by defects in genes and morphological abnormalities. The early morphological changes of the process are called 'dysplasia'. Dysplasia is defined as an unequivocal neoplastic (premalignant) transformation confined within the basement membrane. For most Western pathologists malignancy is defined as invasion and characterized by a breach through the basement membrane. Japanese pathologists rely on cytological atypia and complex branching of crypts. Cytological and architectural abnormalities allow identification of dysplasia on routinely stained sections. A distinction is made between low- and high-grade dysplasia. The differential diagnosis between low-grade dysplasia and reactive changes can be difficult. Therefore a second opinion is strongly recommended, not only for high-grade dysplasia but also for low-grade. Immunohistochemistry for p53 and flow cytometry for detection of aneuploidy can support the diagnosis. Identification of dysplasia and malignancy depends on the number of biopsy samples examined. The minimum number of biopsies required has not yet been determined and depends partly on the length of the metaplastic segment. It has been proposed to sample with four quadrant biopsies at 20-mm intervals. New endoscopic techniques can increase the diagnostic yield. Endoscopically visible lesions increase the risk of finding malignancy. The time sequence for the progression of dysplasia is not known but progression from low- to high-grade and cancer has been shown to occur over a period of years although it may not be inevitable.     

Cytopathologic features of secondary peripheral ameloblastic carcinoma: A case report

Peripheral ameloblastic carcinoma is an extremely rare odontogenic tumor derived from the remnants of dental lamina and/or mucosal epithelium of the oral mucosa. We present a case of secondary peripheral ameloblastic carcinoma of the mandibular gingiva. The patient was a 71‐year‐old man with gingival swelling and persistent bleeding. Exfoliative cytology revealed cohesive clusters composed of basaloid cells with nuclear atypia and various forms of keratinized cells of dysplastic squamous appearance. Some cell groups had a peripheral palisade. Histology of the biopsy and surgically removed specimens revealed characteristic features resembling squamous cell carcinoma, basal cell carcinoma, and benign follicles of ameloblastoma. These neoplastic structures, as well as proliferation and elongation of the mucosal epithelium, comprised an extensive network. The varied cytopathologic findings may be related to proliferation and transformation of basal cells of the mucosal epithelium toward ameloblastic carcinoma and variable squamous differentiation. Diagn. Cytopathol. 2011;39:354–358. © 2010 Wiley‐Liss, Inc.