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Актуальність. Розглянуті питання класифікації і диференціальної діагностики езофагітів у дітей шкільного віку. Описані найбільш характерні симптоми езофагітів різної етіології. Матеріали та методи. Обстежено 60 дітей шкільного віку, у яких визначалась характерна для езофагіту клінічна симптоматика. Діагноз верифікований ендоскопічно та морфологічно. Результати. За даними ендоскопічного дослідження в усіх дітей були виявлені вогнищева або дифузна еритема та набряк слизової оболонки, у 53,3 % дітей — множинні білуваті нальоти, у 40 % дітей — лінійні ерозії. При морфологічному дослідженні найпоширенішими змінами були: гіперемія судин мікроциркуляторного русла — у 85 % випадків, вакуольна дистрофія епітеліоцитів — у 76,7 % випадків, діапедезні крововиливи — у 63,3 % випадків, деструкція гранул кератогіаліну — у 50 % випадків. Висновки. Для вирішення проблеми діагностики хронічних езофагітів у дітей необхідний підхід з використанням усієї сукупності сучасних методів діагностики, які зможуть допомогти верифікувати правильний діагноз та визначитися з напрямками подальшого лікування. Морфологічне дослідження є обов’язковим та вирішальним при встановленні діагнозу езофагіту.

We report a case of epidermoid metaplasia of the esophageal mucosa that developed in a patient with a long history of esophageal intramural pseudodiverticulosis (EIPD) complicated by candidiasis. The patient, a 69-year-old man, had been treated for about 3 years for EIPD with candidiasis. After candidiasis improved, the development of epidermoid metaplasia of the esophageal mucosa was observed. It comprised longitudinally arranged, multiple, small, whitish flecks with a scaly appearance on the mucosa of the middle to lower esophagus, and pathological examination demonstrated several fine keratohyalin granules in superficial layers of the squamous epithelium. Six months later, candidiasis was almost cured, but these small flecks had slightly increased in size, and pathological examination demonstrated epidermoid metaplasia consisting of a thick, acellular keratin layer and well-developed granular layer beneath it. We considered that chronic candida esophagitis played the principal pathogenetic role in the development of epidermoid metaplasia. EIPD may have provided an environment suitable for the growth of fungi, and mucinous material contaminated by Candida and excreted from the orifices of EIPD may have irritated the mucosa and induced epidermoid metaplasia.

We present a case of so-called butcher’s warts in a meat handler with atopic dermatitis. PCR with direct sequence analysis confirmed the presence of HPV 7 in the hand warts of the patient. Histopathologically, the lesion contained vacuolated cells with centered nuclei, and there were no abundant keratohyalin granules in the granular layer. Clinically, HPV 7-induced warts tend to appear on the hands of meat/fish handlers or cutters in the world. Therefore, meat/fish had been thought to act as a vector for the transmission of HPV 7. In our case, the Japanese patient’s occupation required the handling of meat/fish products, and HPV 7 was found from his hand warts. This evidence indicated that HPV 7 was widely distributed in the world. However, this patient worked in a Japanese restaurant, which required the handling of meat/fish products with tools such as knives and chopping boards. Therefore, we suggested that HPV 7 might be correlated with specific reservoirs.

Keratohyalin granules were discovered in the mid-19th century in cells that terminally differentiate to form the outer, cornified layer of the epidermis. The first indications of the composition of these structures emerged in the 1960s from a histochemical stain for histidine, followed by radioautographic evidence of a high incidence of histidine incorporation into newly synthesized proteins in cells containing the granules. Research during the next three decades revealed the structure and function of a major protein in these granules, which was initially called the ‘histidine-rich protein’. Steinert and Dale named the protein ‘filaggrin’ in 1981 because of its ability to aggregate keratin intermediate filaments. The human gene for the precursor, ‘profilaggrin,’ was reported in 1991 to encode 10, 11 or 12 nearly identical repeats. Remarkably, the mouse and rat genes encode up to 20 repeats. The lifetime of filaggrin is the time required for keratinocytes in the granular layer to move into the inner cornified layer. During this transition, filaggrin facilitates the collapse of corneocytes into ‘building blocks’ that become an impermeable surface barrier. The subsequent degradation of filaggrin is as remarkable as its synthesis, and the end-products aid in maintaining moisture in the cornified layer. It was apparent that ichthyosis vulgaris and atopic dermatitis were associated with the absence of this protein. McLean’s team in 2006 identified the cause of these diseases by discovering loss-of-function mutations in the profilaggrin gene, which led to dysfunction of the surface barrier. This story illustrates the complexity in maintaining a healthy, functional epidermis.

— Two Pugs and two Miniature Schnauzers with multiple pigmented epidermal nevi were investigated. The four dogs had pigmented cutaneous maculae and plaques. Histopathological evaluation showed papillated or digitated epidermal hyperplasia with hypermelanosis and giant keratohyalin granules in the stratum granulosum. Immunohistochemical staining revealed papillomavirus group-specific antigen in the skin specimens from all four dogs. Electron microscopic study of the specimens from two dogs revealed numerous round viral particles within the nuclei of the keratinocytes in the upper stratum granulosum. It was suspected that papillomavirus was the etiologic agent of the lesions, and that Pugs and Miniature Schnauzers might be predisposed to infection. These findings indicate this canine dermatosis resembles epidermodysplasia verruciformis (EV) of humans, a rare chronic disease caused by human papillomavirus. The potential for transformation of the lesions to squamous cell carcinoma is also suspected and discussed. Resume— Deux Carlins et deux Schnauzers nains presentant de multiples naevi epidermiques pigmentes sont examines. Les quatre chiens presentent des macules et des plaques pigmentees. Les lesions histopathologiques montrent une hyperplasie epidermique papillaire ou digitee avec une hypermelanose et la presence de grains de keratohyaline dans le stratum corneum. Les colorations immunohistochimiques revelent des antigenes specifiques du groupe des papillomas virus dans les biopsies des quatre chiens. L'etude ultrastructurale a partir des biopsies de deux chiens montrent de nombreuses particules virales rondes dans les noyaux des keratinocytes des couches superieures du stratum granulosum. II a ete suspecte que le papilloma virus etait l'agent causal des lesions et que les Carlins et les Schnauzers nains pouvaient etre predisposes a cette infection. Ces elements font que cette dermatose observee chez le chien ressemble a l'epidermodysplasie verruciforme de l'homme, une dermatose chronique rare causee par un papilloma virus humain. La potentialite de transformation des lesions en epithelioma spinocellulaire est aussi suspectee et discutee. [Nagata, M., Nanko, H., Moriyama, A., Washizu, T., Ishida, T. Pigmented plaques associated with papilloma virus infection in dogs: Is this epidermodysplasia verruciformis? (Plaques hyperpigmentees associees a une infection a papilloma virus chez le chien: est-ce epidermodysplasie verruciforme?). Resumen— Se investigo dos perros de raza Pug y dos de raza Schnauzer Miniatura con multiples nevos epidermicos pigmentados. Los cuatro perros presentaban maculas y placas cutaneas pigmentadas. El estudio histologico mostro hiperplasia epitelial con papilas y digitaciones, asi como hipermelanosis y granules de queratohialina gigantes en el estrato granuloso. Las tinciones immunohistoquimicas detectaron antigeno grupo-especifico de papilomavirus en las muestras de los cuatro animales. Mediante estudios de microscopia electronica en muestras de dos de los perros se observaron numerosas particulas virales redondas en el nucleo de los queratinocitos mas superficiales del estrato granuloso. Se sospecho que Papilomavirus era el agente etiologico de estas lesiones y que los Pugs y los Schnauzer Miniatura podrian estar predispuestos a la infeccion. Estos hallazgos indican que esta dermatosis canina es parecida a la Epidermodisplasia Verruciforme (EV) de la especie humana, una enfermedad cronica rara causada por el Papilomavirus Humano. Se sospecha y discute la posible transformacion de estas lesiones a carcinoma de celulas planas. [Nagata, M., Nanko, H., Moriyama, A., Washizu, T., Ishida, T. Pigmented plaques associated with papilloma virus infection in dogs: Is this epidermodysplasia verruciformis? (Placas pigmentadas asociadas con infeccion por papillomavirus en el perro: se trata de epidermodisplasia verruciforme?)

Central to forming and sustaining the skin’s barrier, epidermal keratinocytes (KCs) fluxing to the skin surface undergo a rapid and enigmatic transformation into flat, enucleated squames. At the crux of this transformation are intracellular keratohyalin granules (KGs) that suddenly disappear as terminally differentiating KCs transition to the cornified skin surface. Defects in KGs have long been linked to skin barrier disorders. Through the biophysical lens of liquid-liquid phase separation (LLPS), these enigmatic KGs recently emerged as liquid-like membraneless organelles whose assembly and subsequent pH-triggered disassembly drive squame formation. To stimulate future efforts toward cracking the complex process of skin barrier formation, in this review, we integrate the key concepts and foundational work spanning the fields of LLPS and epidermal biology. We review the current progress in the skin and discuss implications in the broader context of membraneless organelles across stratifying epithelia. The discovery of environmentally sensitive LLPS dynamics in the skin points to new avenues for dissecting the skin barrier and for addressing skin barrier disorders. We argue that skin and its appendages offer outstanding models to uncover LLPS-driven mechanisms in tissue biology.

Liquid-liquid phase separation (LLPS), the unmixing of inhomogeneous fluids into two or more phases, is emerging as a paradigm for the formation of a myriad of membraneless compartments inside cells (1, 2). This type of spatial organization, in contrast to membrane-bound compartmentalization, has long lacked unifying principles. However, the physiological relevance of compartmentalization through LLPS inside cells is still poorly understood and often speculative. Additionally, regulatory mechanisms through which cells control and exploit LLPS are still emerging. On page 1210 of this issue, Garcia Quiroz et al. (3) show that keratohyalin granules (KGs) that are formed during epidermal differentiation in the skin are pH-sensitive liquid-like protein condensates. Formation of KGs may be physiologically important because mutations that cause defects in this process are associated with the common skin barrier defect ichthyosis vulgaris.

Epidermal stratification critically depends on keratinocyte differentiation and programmed death by cornification, leading to formation of a protective skin barrier. Cornification is dynamically controlled by the protein filaggrin, rapidly released from keratohyalin granules (KHGs). However, the mechanisms of cornification largely remain elusive, partly due to limitations of the observation techniques employed to study filaggrin organization in keratinocytes. Moreover, while the abundance of keratins within KHGs has been well described, it is not clear whether actin also contributes to their formation or fate. We employed advanced (super-resolution) microscopy to examine filaggrin organization and dynamics in skin and human keratinocytes during differentiation. We found that filaggrin organization depends on the cytoplasmic actin cytoskeleton, including the role for α- and β-actin scaffolds. Filaggrin-containing KHGs displayed high mobility and migrated toward the nucleus during differentiation. Pharmacological disruption targeting actin networks resulted in granule disintegration and accelerated cornification. We identified the role of AKT serine/threonine kinase 1 (AKT1), which controls binding preference and function of heat shock protein B1 (HspB1), facilitating the switch from actin stabilization to filaggrin processing. Our results suggest an extended model of cornification in which filaggrin utilizes actins to effectively control keratinocyte differentiation and death, promoting epidermal stratification and formation of a fully functional skin barrier.

Reticulate scales develop as radial symmetrical anlagen, in contrast to scuttate scales which appear initially as "epidermal placodes." Unlike scuttate scales whose outer and inner epidermal surfaces elaborate β-and α-type keratins, respectively, reticulate scales elaborate only one type of epidermal surface which has been reported to give an α-type, X-ray diffraction pattern. We find that, histologically and ultrastructurally, this surface differs from either epidermal surface of scuttate scales. The keratinizing cells become filled with long interweaving bundles of α-filaments which aggregate into rather homogeneous α-fibrils. Keratohyalin granules, which have been shown to be associated with other keratinizing regions in the bird, do not form during the keratinization of reticulate scale epidermis.

Fundaments: Epidermolytic palmoplantar keratoderma (EPPK), Vorner type (EPPK, OMIM 144200), rare autosomal dominant genodermatosis, first described by Vorner in 1901, is the most common form of diffuse keratoderma clinically characterized by the total area of hyperkeratosis on palms and soles. It is usually due to a dominant mutation in the keratin 9 gene (KRT9), located in chromosome 17, which is specific for the palmoplantar skin.Case report: A two-year-old boy presenting hyperkeratosis of palms and soles since the first month of birth. Diffuse hypertrophic plaques with yellowish keratosis and fissures limited to palms and soles, and distinct erythematous margin at the border of normal-appearing skin, were noticed. A punch biopsy of the palms showed epidermolysis in spinous and granular layers, hyperkeratosis and irregular clumped keratohyaline granules. Discussion: EPPK integrates a complex group of uncommon keratodermas, mainly based on the morphologic and topographical characteristics, and associated systemic alteration. It is the most frequent form of such diseases and usually appears during the first weeks or months after birth, characterized by diffuse thickening of the skin of palms and soles with well-circumscribed erythematous borders. This disease may be followed by other ones, above all neoplasias, and probably arises due to segregation of oncogenes. Histopathologically, EPPK presents the characteristic features of epidermolytic hyperkeratosis and vacuolar cytolysis in the upper spinous and granular layers, large irregularly shaped keratohyalin granules and hyperkeratosis, and electron microscopy shows vacuolization of keratinocytes of the granular layer and clumping of keratin filaments. It is differentiated from other palmoplantar keratodermas by the lack of other cutaneous findings and by the presence of histologic features of epidermolytic hyperkeratosis. Currently, there are few therapeutic resources, which are mostly symptomatic. RNA interference strategies are being investigated as an approach to allele-specific gene silencing for dominant-negative keratin diseases.

Ankyloblepharon-ectodermal defects-cleft lip/palate (AEC) syndrome, also known as Hay-Wells syndrome, is a rare autosomal dominant disorder characterized by congenital ectodermal dysplasias and is caused by mutations in p63 [1, 2]. Six isoforms are generated from the p63 gene and the main isoform expressed in postnatal skin is ΔNp63α, which functions as a key regulator of epidermal integrity. Mutations identified in AEC syndrome localize in sterile α motif and transactivation inhibitory domains [...]

Background: Pitted keratolysis (PK) is a superficial cutaneous infection caused by different species of bacteria. It is characterized by discrete crateriform and malodorous pits and erosions coalescing to form bizarre figures on the soles. Objective: To investigate the process of corneocyte shedding in PK. Method: Biopsies from typical lesions of 3 patients were investigated by transmission electron microscopy. Results: Microorganisms were found both inter- and intracellularly in corneocytes and keratinocytes of the upper layers of the stratum spinosum. Bacteria exhibited different morphologic aspects related to their localization in the epidermis. Keratohyalin granules were strikingly abnormal, showing sharp segregation between rounded dense areas and more electron-translucent areas. Some keratohyalin granules exhibited only alveolar dense areas. These altered keratohyalin granules were still present inside corneocytes. The corneodesmosomes at the bottom of the pits were in part cleaved leading to partial corneocyte dissociation. Conclusion: It is suggested that proteases secreted by the bacteria alter the structure of both the corneodesmosomes and the keratohyalin granules. The latter appeared more resistant to the normal processing of profilaggrin inside the corneocytes.

Comparative study of the epidermis of lepidosaurian reptiles helps us to understand the formation of the shedding complex which determines epidermal shedding. The present ultrastructural study has analyzed the complete sequence of epidermal differentiation in the agamine lizard Physignatus lesueurii from 1 to 80 days post-hatching. Beneath a β-layer 20–40 layers of cells with an α-pattern of keratinization are produced, starting from narrow cells (mesos-like) followed gradually by typical thicker α-cells. At 80 days post-hatching an α-layer is still forming and the first epidermal shedding has still to take place. The differentiation of a shedding complex has been studied on the epidermis at 38 and 64 days of tail regeneration. Beneath the superficial regenerating (wound) epidermis, cells of the clear layer contain a meshwork of coarse and fibrous filaments which appear to turn into large keratohyalin-like granules. This extensive cytoskeleton may determine the progressive hardening of clear cells that function as a template for the formation of the large microornamentations of the underlying layer, a process that might be generalized for the genesis of microornamentations in all lepidosaurian reptiles. The microornamentations in Physignatus have a honey-comb pattern and are produced by the fusion between ‘oberhautchen” and β-cells.

In order to investigate the re-epithelialization process during wound healing, the hair on the back of guinea pigs was shaved and then excisional wounds were made through the entire thickness of the skin. Histological changes were observed and changes in the expression of different cytokeratin polypeptides were examined using an immunohistochemical technique. Immunohistochemical study revealed that the proliferating and migrating keratinocytes expressed the same cytokeratins as the basal cells of normal epidermis. In addition, the entire epidermis of fairly remote areas from the edges of the wound where no thickening was observed showed a temporarily abnormal staining pattern. The suprabasal cells in the regenerating epidermis temporarily expressed cytokeratins not only specific for suprabasal cells but also specific for basal cells. The cytokeratins expressed in normal basal keratinocytes were also present in the thickened granular layers. These data indicate that the expression of cytokeratins in the epidermal keratinocytes (even in fairly remote areas from the wound edges) changes during wound healing, that the origin of the migrating keratinocytes from the remaining epidermis seems to be the basal cells in the epidermis, and that the appearance of keratohyalin granules is not related to changes in cytokeratin expression.

Summary Light and electron microscopic observations of the dorsal lingual epithelium of the crab-eating monkey, Macaca irus , revealed three different regions: the epithelium on the anterior side of the filiform papillae, the epithelium on the posterior side of the filiform papillae, and the interpapillar epithelium. Whereas the basal and suprabasal cells are similar throughout, differences characterize the intermediate and surface layers. Keratohyalin granules appear predominantly in the intermediate layer of the epithelium on the anterior side of filiform papillae. In the epithelium on the posterior side of the filiform papillae, no keratohyalin granules are seen and, instead, tonofibrils are prominent. The cells begin to be sigificantly flattened. In the interpapillar epithelium, no keratohyalin granules and tonofibrils are seen, and the tonofilaments occupy almost the entire cytoplasm of the cells of the intermediate and surface layers, with the cells having larger volumes in these layers.

Recent biochemical and morphological investigations have provided evidence for a heterogeneous composition of keratohyalin in human skin. A major component is filaggrin. In interfollicular epidermis the heterogeneity of keratohyalin is not directly visible, whereas in normal ridged skin bicomponent keratohyalin is revealed by electron microscopy. Skin biopsies of ridged and non-ridged skin of normal individuals and patients with autosomal dominant ichthyosis vulgaris (ADI) — characterized by defective keratohyalin synthesis and lack of filaggrin — were investigated by routine transmission electron microscopy and immunogold postembedding techniques using a commercial monoclonal anti-filaggrin antibody. In normal interfollicular epidermis filaggrin labelling was demonstrated on keratohyalin granules and in the lowermost cornified cells, whereas in ADI patients crumbly keratohyalin granules were present that did not show specific labelling for filaggrin. In normal ridged skin only the major (more electron-dense) component reacted with anti-filaggrin, whereas the attached (less electron-dense) component did not react. Ridged skin of ADI patients contained globular keratohyalin that did not react with anti-filaggrin, thus corresponding to the attached keratohyalin component in normal ridged skin. Our results provide a visible counter-part to the recent biochemical investigations of keratohyalin protein heterogeneity and contribute to the understanding of terminal differentiation in human skin and of the defective keratohyalin synthesis in ADI.

Summary An unusual ichthyosiform dermatosis with circumscribed areas of blistering hyperkeratoses as well as scaly areas was observed in five consecutive generations of a German family. Light and electron microscopical studies revealed oedema of the keratinocytes in the upper epidermis but no defects of tonofilaments and keratohyalin granules. We suggest that this type of ichthyosis exfoliativa inherited as an autosomal dominant trait represents a new and distinct entity.

Here, we report a case of a middle-aged woman presenting with severe, long-standing, hyperkeratotic plaques of the lower extremities unrelieved by over-the-counter medications. Initial history and clinical findings were suggestive of an inherited ichthyosis. Ichthyoses are genetic disorders characterized by dry scaly skin and altered skin-barrier function. A diagnosis of ichthyosis vulgaris was confirmed by histopathology. Etiology, prevalence, and treatment options are discussed.

These outgrowths resembled transversally cut logs (Fig. 2). The largest were from 2 to 3 cm in height and their base ranged from 1 to 2 cm in diameter. The palms and soles 'were thickened but did not show these excrescences. The scalp, face, nails, and genitalia were unaffected. HJstopathologic examination revealed marked hyperkeratosis and acanthosis. The granular layer was prominent and vacuolated with fragmentation of the keratohyalin granules. The stratum malpighii was edematous. There was a mild inflammatory infiltrate in the papillary dermis.

Peeling skin syndrome is a rare dermatosis characterized by spontaneous and painless peeling of the skin. The authors report two patients with history of spontaneous, asymptomatic, and noninflammatory peeling skin of the acral surfaces after soaking in water. On light microscopy, blisters were located in the mid layers of the stratum corneum, above the granular layer. Ultrastructural examination revealed increased intercellular lipids and abnormal, "moth-eaten," keratohyalin granules, but the authors were unable to determine whether the separation initiated within the horny cells or between adjacent cells. These patients represented a localized variant of peeling skin syndrome.

Background: Granular parakeratosis is a hyperkeratotic eruption of unknown etiology that occurs in the axilla and other intertriginous areas. The histologic features are unique for the retention of keratohyalin granules in the stratum corneum. Objective: The aim of the article is to review the clinical manifestations and treatment of granular parakeratosis. Methods: A case report and literature review are presented. Results: Twenty-six cases of granular parakeratosis now have been reported and reviewed. Conclusion: Granular parakeratosis occurs predominantly in middle age women and most frequently in the axilla. A number of treatments have been applied to the 26 cases reported to date, without consistent responses. No evidence-based therapy can be suggested at present.

Peeling skin syndrome is a rare autosomal recessive disease characterized by widespread painless peeling of the skin in superficial sheets. We describe a 34-year-old man with a lifelong history of spontaneous asymptomatic peeling skin limited to the acral surfaces. This patient probably represents a localized variant of peeling skin syndrome, which has previously been described as a generalized condition. Light and electron microscopic studies of biopsy specimens taken before and after immersion in water were performed. It was concluded that this patient has abnormal keratohyalin granules and inadequate aggregation of keratin filaments that caused the separation of the epidermis in the stratum corneum through the clear zone. Alternatively, unknown keratin species expressed in the clear zone may also cause the abnormality. (J Am Acad Dermatol 2000;43:1112-9.).

In this report, we describe a 2.5-year-old severely mentally retarded boy with peculiar appearance and generalized ichthyosis, born to consanguineous Turkish parents. The histological finding in the skin biopsy of unusually large oval keratohyalin granules in the granular cells is unique, and hitherto has not been reported in other ichthyosis-mental retardation syndromes.

Rupture, abscess formation, and re-encapsulation is the key sequence which underlies the creation of secondary comedones. These can arise only when rupture is partial, and generally not from nodules. Substantial segments of comedonal epithelium must survive the inflammatory storm. Because focal rupture and re-encapsulation may happen once or many times, secondary comedones cannot be placed in such neat categories as primary ones; they are exceedingly variable in size and shape. Some of them may look like closed or open comedones. Secondary comedones can be identified with certainty only by histological examination.

Forty warts from different patients and of different clinical type were examined histologically and virologically. Eight lesions were found to be associated with human papillomavirus type 1 (HPV 1), 15 tumors were induced by HPV 2, HPV 3 was detected 4 times, HPV 4 twice, and HPV 6 eleven times. HPV 3, HPV 4, and HPV 6 induced warts revealed a correlation between histology and virus type. They are characterized by the so called "edematous type clear cells". In HPV 3 associated flat warts pycnotic nuclei were mainly localized in the center of large vacuoles. In genital warts sickle shaped nuclei were pushed to the margin of the vacuolized cells. The histology of HPV 1 and HPV 2 induced warts was more heterogenous. With one exception HPV 1-induced lesions represented typical myrmecia warts, varying in the number and shape of inclusion bodies. HPV 2 associated common warts, however, revealed 3 very distinct histologic features: (1) Inclusion wart typical for HPV 1, (2) Classical common wart with marked condensation of keratohyalin granules, (3) Warts with extreme vacuolization of squamous and granular cells leading to a honeycomb-like picture.

Eight patients with psoriasis (pustular, erythrodermic or severe plaque type) were treated successfully with retinoid (Ro 10-9359) or with retinoid followed by PUVA (RePUVA). The histological changes in recovering skin were examined during 14 weeks. Treatment resulted in normalization of keratinocyte differentiation with fine structural changes suggesting decreased metabolic activity and a reduction of mitoses. There was an increase in the number of keratohyalin granules and of tonofilaments and desmosomes and a decrease in leukocytes in the epidermis. The different cell organelles were studied in detail, but the exact mechanism of retinoid action remains unsolved. Although the treatments were clinically highly effective, total normalization of the histological and electron microscopical picture was not achieved.

We used Rhodamin B stain in sections of normal skin, benign and malignant epithelial tumors and dermatoses. Keratin staining was uneven and showed variation in different lesions. While tricho-hyalin of the anagen hair follicle stained with intensity, keratohyalin granules failed to show similar reaction.

In order to clarify the site(s) from which steatocystoma multiplex (SCM) originates, five cases of SCM and the normal pilosebaceous apparatus were comparatively examined by electron microscopy. The cyst-wall of SCM, consisting either of flattened or of undulating horny layer, contained a small number of tonofilaments, desmosomes, and tiny spherical keratohyalin granules. There were variable numbers of lamellar granules which were also frequently observed in the intercellular spaces of the horny layer. Three of the SCM cases included sebaceous cells. The contents of the cysts were mostly amorphous and short-fibrillar, but sometimes keratinized cells and remnants of lamellar granules were observed. These findings were analogous to those of the normal pilosebaceous apparatus from the level of the lower part of the infundibulum to the outer root sheath Via the sebaceous duct, and were specifically more analogous to those of the sebaceous duct.

The pool of free amino acids, urocanic acid and pyrrolidone carboxylic acid in mammalian stratum corneum has been shown to be derived principally or totally from the histidine-rich protein of the keratohyalin granules. The time course of appearance of free amino acids and breakdown of the histidine-rich protein are similar, as are the analyses of the free amino acids and the histidine-rich protein. Quantitative studies show that between 70 and 100% of the total stratum corneum-free amino acids are derived from the histidine-rich protein.

Subcultivated rat lingual epithelial cells when grown on collagen gels at a liquid-gas interface achieve a highly ordered state that closely resembles the parent tissue. Three distinct cell layers are present; basal, spinous, and keratinized. Basal cells are cuboidal in shape and form a complex interface with the underlying collagen fibrils. Spinous cells form a layer 5–10 cells thick and, with the exception of keratohyalin granules, possess an organellar complement identical with native cells, including membrane-coating granules. The keratinized cell layer increases in thickness as a function of time spent in culture. Forty or more plies of terminally differentiated cells are observed following a 30-day culture period. Terminally differentiated cells while retaining pycnotic nuclei and some other organellar debris are principally envelope-enclosed squames filled with tonofilaments. Keratinization is a continuing process which occurs simultaneously across the full expanse of the culture surface. The high degree of tissue organization observed appears to be the result of feeding the cultures from the undersurface.

A pronounced species variation in the organization of filiform papillae has been observed. Preliminary histologic studies of cat tongue revealed marked regional variations in size, shape and organization of filiform papillae. Therefore, a correlated light microscopic, transmission and scanning electron microscopic study of tissue samples of representative areas of the cat tongue was undertaken for further elucidation. Results showed that filiform papillae on the tip of the tongue were short and exhibited several conical processes from the base of each papilla. In contrast, filiform papillae in the midportion of the dorsum of the tongue consisted of a large mound with a single sharp spinous process projecting posteriorly. In the region of the vallate papillae, the filiform papillae were shorter and more conical than those on the midportion of the tongue. In addition, keratohyalin granules in filiform papillae were comprised of an eosinophil spheroid with small basophil attachments.

We report a case of multiple minute digitate hyperkeratosis. The patient had hundreds of keratotic lesions--some tiny and spiked, others larger, flat papules--localized on the trunk and arms. Histologic sections showed focal areas of compact hyperorthokeratosis with few dermal changes. Ultrastructurally, keratohyalin granules were smaller than normal. The keratin pattern was one of a normal variant. Odland bodies present. Various family members of the patient, in different generations, were affected.