Trichoblastoma is a benign cutaneous neoplasm that consists of follicular germinative cells. We report a case of trichoblastoma in a 58-year-old man. The tumor was presented as a solitary symmetrical shaped pedunculated 5.0x4.0x2.0cm sized multilobular tumor on right lower leg for 2 years. Histopathologic examination showed well circumscribed dermal tumor composed of multilobular tumor islands of palisaded basaloid epithelial cells. The tumoral lobules were concentrically surrounded by hyalinized collagen bundles with fibroblasts. The overall architecture was reminiscent of hair bulbs. Cytokeratin 14 stain showed positive reaction, but cytokeratin 10 stain showed negative reaction. The tumor was completely excised with clear margin. No sign of recurrence has been noted until 9 months later.
Collagen ; Epithelial Cells ; Fibroblasts ; Hair ; Humans ; Hyalin ; Islands ; Keratin-14 ; Keratins ; Leg ; Middle Aged ; Recurrence

A 42-year-old man without any signs or symptoms of illness underwent esophagogastroduodenoscopy (EGD) for a routine health check up. On esophagogastroduodenoscopy, multiple small and yellowish mucosal plaques were detected in the mid to distal esophagus. These plagues proved to be ectopic sebaceous glands of the esophagus according to the histologic examination. On the immunohistochemical staining with anti-Keratin 14, the basal cells and the heterotopic sebaceous glands were immunoreactive for keratin 14. The histogenesis of this extremely rare lesion is not completely clear. There have been some reports on ectopic esophagus sebaceous glands combined with esophageal cancer or gastric cancer. However, malignant transformation of the ectopic sebaceous gland itself has not yet been reported on. This case was regularly followed up for 12 months, and no interval change or malignant transformation was found both endoscopically and histologically.
Adult ; Endoscopy, Digestive System ; Esophageal Neoplasms ; Esophagus ; Humans ; Keratin-14 ; Sebaceous Glands ; Stomach Neoplasms

Stem/progenitor cells are important for salivary gland development, homeostasis maintenance, and regeneration following injury. Keratin-14⁺ (K14⁺) cells have been recognized as bona fide salivary gland stem/progenitor cells. However, K14 is also expressed in terminally differentiated myoepithelial cells; therefore, more accurate molecular markers for identifying salivary stem/progenitor cells are required. The intraflagellar transport (IFT) protein IFT140 is a core component of the IFT system that functions in signaling transduction through the primary cilia. It is reportedly expressed in mesenchymal stem cells and plays a role in bone formation. In this study, we demonstrated that IFT140 was intensively expressed in K14⁺ stem/progenitor cells during the developmental period and early regeneration stage following ligation-induced injuries in murine submandibular glands. In addition, we demonstrated that IFT140⁺/ K14⁺ could self-renew and differentiate into granular duct cells at the developmental stage in vivo. The conditional deletion of Ift140 from K14⁺ cells caused abnormal epithelial structure and function during salivary gland development and inhibited regeneration. IFT140 partly coordinated the function of K14⁺ stem/progenitor cells by modulating ciliary membrane trafficking. Our investigation identified a combined marker, IFT140⁺/K14⁺, for salivary gland stem/progenitor cells and elucidated the essential role of IFT140 and cilia in regulating salivary stem/progenitor cell differentiation and gland regeneration.
Animals ; Carrier Proteins/metabolism* ; Cell Differentiation ; Keratin-14/metabolism* ; Mice ; Osteogenesis ; Salivary Glands/metabolism* ; Stem Cells

Adenoma, Sweat Gland ; metabolism ; Diagnosis, Differential ; Humans ; Keratin-14 ; metabolism ; Keratin-17 ; metabolism ; Keratin-18 ; metabolism ; Keratin-7 ; metabolism ; Keratins ; metabolism ; Papilloma ; metabolism ; Sebaceous Gland Neoplasms ; metabolism ; Skin Neoplasms ; metabolism ; Sweat Gland Neoplasms ; metabolism

Using immunohistochemical staining for alpha-smooth muscle actin (alpha-SMA), glial fibrillary acidic protein (GFAP), S100 protein (S100), p63, cytokeratin 14 (CK14), and cytokeratin 19 (CK19), we studied acinar and myoepithelial cells of major and minor salivary glands obtained from 14 donated cadavers (78-92 years old) and 5 donated fetuses (aborted at 15-16 weeks of gestation). CK and p63 expression was investigated only in the adult specimens. SMA was detected in all adult glands as well as in fetal sublingual and pharyngeal glands. GFAP expression was seen in a limited number of cells in adult glands, but was highly expressed in fetal pharyngeal glands. S100-positive myoepithelial-like cells were present in adult minor glands as well as in fetal sublingual and pharyngeal glands. Expression of p63 was evident in the ducts of adult glands. CK14 immunoreactivity was observed in a limited number of glandular cells in adults, in contrast to consistent expression of CK19. In both adults and fetuses, a mosaic expression pattern was usually evident for each of the examined proteins. A difference in immunoreactivity for the nerve markers GFAP and S100 was observed between the major and minor glands. Thus, in the present histologic study, we distinguished between the specific gland types on the basis of their immunohistochemical staining. A mosaic expression pattern suggested that the immunoreactivity against nerve protein markers in myoepithelial cells could not be due to the persistence of neural crest remnants or the physiological status of the gland, such as age-related degeneration.
Actins ; Adult ; Aged ; Cadaver ; Fetus ; Glial Fibrillary Acidic Protein ; Humans ; Immunohistochemistry ; Keratin-14 ; Keratin-19 ; Muscles ; Neural Crest ; Population Characteristics ; Proteins ; Salivary Glands ; Salivary Glands, Minor

Epidermolysis bullosa simplex (EBS), an inherited genetic disorder, is most often caused by a dominant-negative mutation in either the keratin 5 (KRT5) or the keratin 14 (KRT14) gene. These keratin mutants result in a weakened cytoskeleton and cause extensive cytolysis. It is important to analyze the KRT5 or KRT14 genes of the patient and their family members by mutational analysis in order to identify genetic defects as well as the need for genetic counseling. In this study, we present a 5-year-old Korean boy who had been developing blisters and erosions on the palms of his hands and soles of his feet since infancy. In addition, while his younger sister and father showed similar clinical manifestation, his mother did not. The patient was diagnosed with EBS based on clinical manifestation, which is characterized by the presence of blisters restricted to the palms and soles, histological findings, and mutational analysis. Mutational analysis of the patient's DNA revealed a thymine-to-cytosine transition at codon 608 in the KRT-5 gene, resulting in a leucine-to-proline substitution in the keratin 5 protein. The same mutation was identified in the paternal, but not maternal, DNA. Here, we report a case of Weber-Cockayne type EBS with vesicles and bullae restricted to the palms and soles with a novel, paternally inherited mutation in KRT5 gene (exon2, c.608T>C).
Blister ; Child, Preschool ; Codon ; Cytoskeleton ; DNA ; Epidermolysis Bullosa Simplex* ; Fathers ; Foot ; Genetic Counseling ; Hand ; Humans ; Keratin-14 ; Keratin-5* ; Male ; Mothers ; Siblings

OBJECTIVETo identify keratin 5 (K5) and keratin 14 (K14) gene mutations in a family affected with epidermolysis bullosa simplex with mottled pigmentation.

METHODSGenomic DNA was extracted from peripheral blood samples obtained from eleven patients from the family and controls. All the exons of K5 and K14 genes were amplified using polymerase chain reaction (PCR) and directly sequenced.

RESULTSBy DNA sequence analysis, a missense mutation in K5 gene (c.237C>T) was detected. The same mutation was not found in non-affected members from the family and normal controls.

CONCLUSIONMutation in K5 gene (c.237C>T) may be responsible for the development of disease in this family.

Base Sequence ; DNA Mutational Analysis ; Epidermolysis Bullosa Simplex ; genetics ; pathology ; Exons ; Female ; Humans ; Hyperpigmentation ; genetics ; pathology ; Keratin-14 ; genetics ; Keratin-5 ; genetics ; Male ; Mutation ; Pedigree ; Sequence Analysis, DNA

Epithelial differentiation and morphogenesis in skin and oral mucosa were elucidated using various experimental tools. However, tongue epithelial differentiation has not been examined properly yet. In this study, we identified the relationship between morphological changes and localizations of differentiation markers, such as cytokeratins and PAX 9 in mice embryonic tongue development. Protective barrier formation and localization pattern of cytokeratins in tongue epithelium were examined with toluidine blue staining and immunohistochemistry respectively. Localization patterns of PAX 9 and Cytokeratin 14 were coincided during tongue epithelium development. In addition, compared with Ki67 localizations, marker for cell proliferation, localization patterns of PAX 9 and Cytokeratin 14 would suggest that these factors would involve in tongue barrier formation through cell proliferation. Based on these results, tongue epithelial differentiation would begin at E14 with the specific localizations of PAX 9 and Cytokeratin 14 prior to protective barrier formation then Cytokeratin 1, keratinization marker, would involve in protective barrier and filiform papillae formations.
Animals ; Antigens, Differentiation ; Cell Proliferation ; Epithelium ; Immunohistochemistry ; Keratin-14 ; Keratins ; Mice ; Morphogenesis ; Mouth Mucosa ; Skin ; Tolonium Chloride ; Tongue

PURPOSE: Actinic keratosis (AK) is an incipient form of cutaneous squamous cell carcinoma (SCC). We determined if the pattern of expression of keratin-14 (K14) is a factor for tumor progression in AK and SCC. MATERIALS AND METHODS: Eighteen sections from the tissues of 16 patients were stained with anti-K14 antibody and p16(INK4a). Among the 16 patients, 4 were diagnosed with both SCC and AK at the same site, but AK developed first and SCC developed subsequently. Thus, SCC may have evolved from AK. The other 12 patients were only diagnosed with AK. RESULTS: In all of the AK and SCC tissues, basement membranes showed positive staining for K14. However, strong reactivities were shown in the spinous and granular layers and focuses of dermal invasion in the SCC tissues developed from AK. Two and 3 of the 12 AK cases had moderately positive reactions for K14 in the spinous and granular layers, respectively. Also, all SCC tissues except one had moderate-to-strong reactions in the basal, spinous, and granular layers for p16(INK4a). Two of the 12 AK cases had weak-to-moderate positive reactions in the basal, spinous, and horny layers for p16(INK4a). CONCLUSION: The results of our study advance our understanding of the pathogenesis of SCC developing from AK. The results also indicate a differential role in the control of K14 in normal epithelia, AK, and SCC. K14 expression in the spinous and granular layers may be a prognostic factor for tumor progression of AK.
Actins ; Basement Membrane ; Carcinoma, Squamous Cell ; Cyclin-Dependent Kinase Inhibitor p16 ; Humans ; Keratin-14 ; Keratosis ; Keratosis, Actinic

In spite of frequent usage of primary human foreskin keratinocytes (HFKs) in the study of skin biology, senescence-induced blockage of in vitro proliferation has been a big hurdle for their effective utilization. In order to overcome this passage limitation, we first isolated ten HFK lines from circumcision patients and successfully immortalized four of them via a retroviral transduction of high-risk human papillomavirus (HPV) E6 and E7 oncogenes. We confirmed expression of a keratinocyte marker protein, keratin 14 and two viral oncoproteins in these immortalized HFKs. We also observed their robust responsiveness to various exogenous stimuli, which was evidenced by increased mRNA expression of epithelial differentiation markers and pro-inflammatory genes in response to three reactive chemicals. In addition, their applicability to cytotoxicity assessment turned out to be comparable to that of HaCaT cells. Finally, we confirmed their differentiation capacity by construction of well-stratified three dimensional skin cultures. These newly established immortalized HFKs will be valuable tools not only for generation of in vitro skin disease models but also for prediction of potential toxicities of various cosmetic chemicals.
Antigens, Differentiation ; Biology ; Foreskin* ; Humans* ; In Vitro Techniques ; Keratin-14 ; Keratinocytes* ; Oncogene Proteins ; Oncogenes ; RNA, Messenger ; Skin Diseases ; Skin* ; Zidovudine