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We noticed intracytoplasmic membranous, annular, or circular structures in the lesion of pemphigus foliaceus and studied these by regular transmission electron microscopy and immunoelectron microscopy. These curvicircular bodies were observed in the preacantholytic keratinocytes of the blister wall as well as in acantholytic cells in 6 out of 6 patients with pemphigus foliaceus. They were absent in samples from 3 patients with pemphigus vulgaris. These structures were about 60-70 nm wide and consisted of 4 electron-dense layers. They were continuous with intact desmosomal structures and gap junctions in the periphery of the keratinocytes. These curvicircular membranous bodies were well labeled with immunogold particles for desmoglein, plakoglobin, connexin 43, and IgG. In contrast to pemphigus vulgaris, splitting of desmosomes through dissolution of intercellular desmoglea was seldom observed in all 6 specimens of pemphigus foliaceus. These findings suggest that in pemphigus foliaceus 1) curvicircular bodies are derived from internalized desmosomes and gap junctions, and 2) cell-to-cell adhesions are weakened by this internalization and acantholysis is initiated, while in pemphigus vulgaris the dissolution of desmoglea is the initial event. It is suggested that in pemphigus foliaceus the binding of autoantibody induces internalization of many intact desmosomes and gap junctions rather than splitting them.

Background: Distinguishing basal cell carcinoma (BCC) from other benign and malignant skin tumors is sometimes a difficult task for the pathologists. Because the activation of hedgehog signals and the up-regulation of its critical transcriptional factor Gli1 are well documented in BCC, a molecular technique measuring Gli1 transcripts may aide the diagnosis. Methods: Gli1 transcript levels were measured by real-time quantitative reverse transcriptase polymerase chain reaction (RT-PCR) using RNA extracted from formalin-fixed, paraffin-embedded tissues of 68 cases of various skin tumors. Hematoxylin and eosin-stained pathology slides were independently reviewed by three expert dermatopathologists. Results: The histological diagnoses were unambiguous in 53 tumors. The tumors included BCC (21), squamous cell carcinoma (13), seborrheic keratoses (8), trichoepithelioma (5), eccrine poroma/porocarcinoma (4), and sebaceous epithelioma/carcinoma (2). In these unambiguous cases, all BCC and trichoepithelioma tumors showed high expression of Gli1mRNA, while the expression was virtually absent in other tumors. The diagnosis was discordant among three pathologists in the remaining 15 tumors. Histological diagnoses included BCC, BCC with sebaceous differentiation, sebaceoma/sebaceous epithelioma, trichoblastoma, trichoepithelioma, basaloid follicular harmartoma, basosquamous carcinoma, etc. Six of them showed high Gli1 transcript levels. Conclusions: Quantification of Gli1 transcripts by RT-PCR is helpful in discriminating BCC and trichoepithelioma from other skin tumors.

The molecular pathogenesis of malignant appendageal tumors is poorly understood. Immunohistochemical staining, polymerase chain reaction (PCR)-based loss of heterozygosity (LOH) and sequencing analyses were performed in a mixed group of 21 sweat gland carcinomas. LOH was mostly confined to the chromosome arm 17p. None of the remaining 17 tumors showed LOH at any loci. Nuclear accumulation of p53 protein was observed in 3 tumors, all of which also showed LOH of 17p. One eccrine gland adenocarcinoma showed allelic loss of 17p and a Cys 176 Arg mutation in the p53 gene. The other three tumors that showed LOH of 17p, however, had wild-type p53 genes. A clear transition from benign eccrine poroma to porocarcinoma that was associated with p53 protein stabilization and allelic loss was observed in one tumor. One eccrine porocarcinoma/undifferentiated adnexal carcinoma showed prominent microsatellite instability, probably reflecting an underlying defect in DNA mismatch repair. Overexpression of erbB-2 was observed in three tumors. The low frequencies of LOH and p53 alterations in sweat gland carcinomas contrasted with the multiple genetic defects normally observed in cutaneous squamous cell carcinomas, and may be partly explained by the relative protection of cutaneous appendages from ultraviolet light and other environmental mutagens.

Six cases of spiny keratoderma were analyzed with hair specific antikeratin antibodies (AE13, AE14) and by electron microscopy. The keratotic column exhibited a different keratin birefringence and the underlying viable epidermis was less eosinophilic than the surrounding epidermis. AE13, which is specific for hair cortex, was positive in the lower column and variably positive in the viable epidermis, often beyond the columnar lesion. AE14 was negative in the lesion. Electron microscopy demonstrated features of keratinization of normal hair cortex, i.e. by the accretion of keratin filaments without production of keratohyalin or trichohyalin granules. Cementsomes (lamellar granules) and marginal bands were not produced as they are not formed in normal cortical keratinization. It was suggested that spiny keratoderma represents an ectopic hair formation of palms and soles.

We report a case of intraepidermal Merkel cell carcinoma which occurred on the face of a 76-year-old white male. This slow-growing tumor was mostly confined in the epidermis and pilosebaceous apparatus where tumor cells spread in a pagetoid fashion forming tumor cell nests. Histologically it resembled a superficial spreading melanoma. A heavy lymphocytic infiltration was seen beneath the epidermal lesion as is often seen in pagetoid melanomas. Histochemical and ultrastructural features such as the presence of cytokeratin 20, synaptophysin, neuron specific enolase, desmosomes, and dense cored granules confirmed the diagnosis of Merkel cell carcinoma. Occasional mitotic cells and many apoptotic cells were found in the tumor. Dylon positive, amyloid depositions were seen in the lower epidermis and papillary dermis; they were probably derived from apoptotic tumor cells. It was thought that apoptosis limited the speed of growth of this tumor. We believe that this is probably the most convincing case of intraepidermal Merkel cell carcinoma originating from epidermal Merkel cells or its precursors (stem cells).

Urokinase-type plasminogen activator (uPA) has been well documented in the development of pemphigus acantholysis. The function of its receptor (uPA-R) in pemphigus acantholysis has only recently attracted attention. Increased expression of uPA-R has been demonstrated in pemphigus vulgaris. In this study, we have further explored the functional involvement of uPA-R in pemphigus acantholysis. Our results show that uPA-R expression is significantly increased in acantholytic foci of pemphigus vulgaris and pemphigus foliaceus but not in bullous pemphigoid or normal skin specimens; the expression of uPA-R in cultured human keratinocytes is subjected to regulation by pemphigus vulgaris IgG but not by pemphigoid IgG or normal human IgG; furthermore, anti-uPA-R monoclonal antibody effectively inhibits pemphigus vulgaris IgG induced acantholysis in skin organ cultures. These data suggest that uPA-R may play an important role in the pathogenesis of pemphigus acantholysis.

The histogenesis of apocrine and eccrine neoplasms has always interested dermatopathologists. In addition, the histologic differential diagnosis of eccrine carcinoma from metastatic adenocarcinoma is of practical importance. We describe a novel monoclonal antibody IKH-4 which stains the eccrine secretory coil, but not the apocrine secretory segment. Positive staining was observed in eccrine hidradenoma, eccrine poroma, eccrine spiradenoma, papillary eccrine adenoma, eccrine hidrocystoma, syringoma, eccrine carcinoma, and in 1 case of syringocystadenoma papilliferum. Negative staining was observed in apocrine adenocarcinoma, hidradenoma papilliferum, erosive adenomatosis of the nipple, and primary and metastatic adenocarcinomas. IKH-4 antibody was useful in differentiating eccrine from apocrine neoplasms and in differentiating eccrine carcinoma from metastatic adenocarcinomas.

It is important to differentiate the collodion baby from harlequin ichthyosis as the latter rarely survives past the first few days of life. Occasionally, babies share features of both disorders and defy a clinical diagnosis. We recently encountered such a baby who initially presented with harlequin-like features, but evolved into lamellar ichthyosis once the keratin cast was shed. Since the routine histology of all these ichthyoses is similar, we used electron microscopy to study serial biopsy specimens from the affected infant on days 7, 14, and 150, and compared them to our own other cases of harlequin ichthyosis and lamellar ichthyosis. Electron microscopic studies of our case revealed that the marginal band of cornified cells of the stratum corneum was absent when the baby exhibited collodion/harlequin ichthyosis features. Another biopsy taken when the clinical picture evolved into lamellar-like ichthyosis, showed a well-formed marginal band in the cornified cells. In harlequin ichthyosis, the marginal band is present at birth. It is suggested that electron microscopy can differentiate severe collodion baby from harlequin ichthyosis at birth using the absence of the marginal band. Previously reported features of harlequin ichthyosis, such as the presence of giant mitochondria and an abnormal formation of the marginal band in luminal villi of acrosyringeal eccrine duct, were absent in our case.

The expression and localization of connexin 43 (Cx43) were investigated in normal human epidermis, pilosebaceous apparatus, basal cell carcinoma, and squamous cell carcinoma by immunofluorescence as well as by immunoelectron microscopy. In the normal epidermis the immunofluorescence was weak in the basal layer, increased in spinous layer and negative in the horny layer. In the sebaceous gland, peripheral lobular cells showed weak cell membrane dotted pattern. Cell membrane and cytoplasmic fluorescence was strong in the central lobular cells. In the lower hair follicle, the cortex, inner and outer root sheath cells showed cell membrane fluorescence. As cortical cells underwent keratinization, they lost Cx43 epitopes. Basal cell carcinoma and squamous cell carcinoma were poorly stained, and eccrine and apocrine glands were unstained. In immunoelectron microscopy, close membrane appositions of typical gap junctions were often observed in the spinous layers of the epidermis and the immunolabeling for Cx43 was seen along the gap junction structures. Circular and long gap junctions often were found in follicular root sheaths and sebaceous glands. Gold particles labeling Cx43 in these gap junctions were found on the gap junctions or localized in the cytoplasm near the gap junction membranes. Basal cell carcinoma and squamous cell carcinoma had a small number of small gap junctions, and gold particles were not only localized to gap junctions but scattered in the cytoplasm. No gap junctions were labeled in eccrine and apocrine glands. These findings confirmed that 1) long, curved or circular membrane appositions found in hair follicle and sebaceous gland are true gap junctions, 2) immature cells such as epidermal basal cells, peripheral germinative cells of sebaceous gland and basal and squamous cell carcinoma cells do not have fully developed gap junctions, and 3) Cx43 or its precursors are present in the cytoplasm as well as on poorly developed gap junctions in these immature cells. Immunofluorescence findings generally corresponded to ultrastructural distribution and structural maturity of gap junctions.

Proteins involved in the formation of desmosomes and simpler adherens junctions were studied in three types of non-immune acantholytic diseases ; specifically, four cases of Grover's disease (GD), one case of Hailey-Hailey's disease (HHD) and one case of Darier's disease (DD), and these were compared to two cases of immune-mediated acantholytic disease pemphigus vulgaris (PV). The proteins studied included : 1. The intracellular desmosomal proteins, desmoplakin I and II and plakoglobin ; 2. The intercellular desmosomal proteins, desmoglein and CD44 ; and 3. vinculin, which is a major intracellular protein of the simpler aherens junctions. In GD, HHD and DD, immunostaining showed a loss of desmoplakin I and II and plakoglobin from the desmosomes, and a diffuse staining in the cytoplasm. In contrast, in pemphigus vulgaris, these proteins seemed intact and were localized to dot-like spots on the cell surface. Also, desmoglein, and CD44 were slightly affected in GD, and moderately affected in HHD and DD. Absence of desmosomal attachment plaques, the lack of labeling with desmoglein in the affected desmosomes and a diffusion of the labels into cytoplasm were demonstrated with electron microscopy using an immunogold technique. In PV, desmoglein III is one of the target antigens for the autoanti-bodies in this disease and was only partially preserved in a small number of lesional cells, while CD44 was mostly preserved. Vin-culin was intact in GD, HHD and DD, but was lost in PV. This study, our previous work, and that of others, suggest that : 1. In GD, HHD and DD, the proteins of the desmosomal attachment plaque are primarily affected ; 2. In PV, the intercellular glycoproteins are primarily involved ; and 3. Simple adherens junctions are intact in GD, HHD and DD, but are damaged in PV.

In a freshly induced blister from transient bullous dermolysis of the newborn, we found in epidermal basal cells structures similar to anchoring fibrils and lamina densa, often in combination. In the upper dermis, collagenolysis and phagocytosis of degenerated collagen fragments were observed. It is concluded that the stellate inclusions previously reported in this disease are prematurely assembled anchoring fibrils and lamina densa. A disturbance of delivery mechanism of precursor materials for anchoring fibrils and lamina densa may cause the deficiency of these structures which are essential for the integrity of dermo-epidermal adhesion. The presence of many normal anchoring fibrils and lamina densa in perilesional skin and their prompt degeneration after rupture of the inclusions previously led us to conclude that lytic enzymes are involved in the formation of blisters in this disease. The new finding of collagen phagocytosis in the lesional dermis seemed to support this contention.

We report the clinical, histological and ultrastructural features of juvenile colloid milium affecting a brother and sister. In this rare condition, translucent papules develop on sun-exposed areas of skin, with onset in childhood. Histologically and ultrastructurally, the papules consist of amyloid-like material derived from epidermal keratonocytes. A review of the literature suggests a possible genetic abnormality that leads to sun-induced degeneration of keratinocytes.

The innermost cell layer of the outer root sheath (IORS) is a special single cell layer located just outside Henle's layer. In situ end-labeling immunohistochemistry for apoptosis showed that labeled cells were most consistently located in the IORS from the suprabulbar portion to the infundibulum of anagen terminal hair follicles of the human scalp. Labeled cells were also sparsely scattered in the middle portion, including the bulge area of the outer root sheath of anagen hair, the regressing lower portion of catagen hair and the bulb of telogen hair. Ultrastructurally, the cells of the innermost layer underwent cellular degeneration through cytoplasmic vacuolization and nuclear pyknosis without keratohyalin production. These were compatible with the morphology of apoptotic cells. These findings confirmed that the innermost cell layer is different from other layers of the outer root sheath, not only by previously demonstrated criteria such as Ki67 immunostainability and characteristic ultrastructure but also by the mode of cell death.

Three selected cases of transient acantholytic dermatosis were studied because of their definitive correlation with sweating due to fever and/ or bed-ridden situations. Biopsy specimens were serially sectioned and acantholysis was found in the acrosyringium or traced to connect to the acrosyringium in all biopsy specimens. Carcinoembryonic antigen (CEA) and eccrine gland-specific monoclonal antibody, IKH-4, were positive in acantholytic cells. Electron microscopy revealed electron dense material filling the lumen of intraepidermal eccrine ducts. This material leaked into lateral intercellular spaces of the luminal cells, passing tight junctions. Marked edema and numerous lysosomes were reminiscent of those found when eccrine acrosyringium is formed in the embryo; this suggested that an occluded and damaged eccrine intraepidermal duct was being rebuilt via lysosomal digestion.

We encountered a patient who complained of many small papules on the neck, shoulders, upper chest and upper back. Biopsy specimens showed complete loss of elastic fibers in the upper dermis including papillary dermis, whereas those of the mid dermis were intact. Electron microscopy revealed that assembly of component fibrils of elastic fibers was loose, and electron dense substance was aggregated in the spaces between these loosely bound subunit Fibrils or along the periphery of abnormal fibers. Dermal phagocytes engulfed abnormal as well as normal elastic fibers. Upper dermal elastolysis is a clinical and histopathological entity different from mid-dermal elastolysis. Ultrastructural changes of the former are essentially similar to those of the latter but much more severe. It is suggested that activated elastophagocytosis of dermal phagocytes may play a role in this disease. Hashimoto K, Tye MJ. Upper dermal elastolysis: A comparative study with mid-dermal elastolysis.

A case of harlequin ichthyosis was studied with electron microscopy. From the basal cell to granular cell layers, keratinocytes contained giant mitochondria (860 nm) which exhibited vesicular cristae. Typical lamellar granules were absent; instead, numerous dense cored granules (DCG) and particles containing cored granules (PCG) were produced. Some of these were discharged into the intercellular spaces of granular cells, but the majority failed to be released from the cytoplasm. These retained DCG and PCG coalesced to form large vacuoles and cavities in the stratum corneum. In the hair follicle, keratinized cells failed to loosen and desquamate into the hair canal; instead, they formed concentric keratin rings surrounding hair, a diagnostic feature of this disease. It is suggested that the abnormal lamellar granule underlies the pathogenesis of this disease and that giant mitochondria may be related to an abnormal lipid metabolism of keratinocytes which may affect lipid composition of lamellar granules.

A typical case of infantile digital fibromatosis (IDF) was studied with antibodies raised against actin, vimentin, desmin and several species of cytokeratin. Strong reactions were observed for desmin, cytokeratin and CK-5, and moderate reactions for vimentin and actin. The diagnostic intracytoplasmic inclusion bodies within the tumor cells were ultrastructurally composed of aggregations of dense microfilaments. Immunoelectron microscopy showed that these filament aggregations are positively stained with anti-actin antibody. From these results, we suggest that the large tumor cell of IDF is a myofibroblast and may originate from or differentiate toward vascular smooth muscle cells, because only this type of smooth muscle can coexpress desmin, vimentin and cytokeratin.

Characteristic moniliform hairs of monilethrix were ultrastructurally examined. By scanning electron microscope, nodes and internodes were seen alternating on the affected hair; the nodes were normal in appearance and thickness, while the internodes were thin and showed ridges and flutes. By transmission electron microscope, the cross sections of the internodes revealed wrinkling of the hair cuticular cells and a reduced number of the cortical cells. Cross sections of the cortical cells per se showed a similar size and a normal keratin pattern in both nodes and internodes, compared with those of control hairs from normal individuals. From these findings, the internodes seemed to be the pathological portions of the moniliform hair, and such abnormal thinning of hair shaft might be caused by a periodical dysfunction of the hair matrix, especially in the hair cortex.

A hair matrix tumor showing an unusual tumor cell arrangement was found at the base of a solitary trichoepithelioma. Coexisting with solid epithelial islands and immature hair follicle-like stroma resembling the Verocay bodies of neurilemmoma or "ripplemarks" on waves were found. In other areas myxomatous degeneration of the stroma changed the rippling into a cribriform pattern. In some parts of the tumor there was a dense melanin pigment associated with MEL5 stained melanocytes. S-100 and CD1 (OKT6) antigen stains demonstrated Langerhans cells scattered in the parenchyma and less frequently in the stroma. The majority of tumor cells were considered immature pilar cortical cells because of the following: 1. HKN-6 was strongly positive; 2. a large number of melanocytes were associated with tumor cells in some foci; 3. ultrastructurally immature tumor cells, which had electron-dense tonofilaments and many desmosomes, were transformed without production of trichohyalin granules into semikeratinized cells which showed nuclear degeneration and loss of electron density in tonofilaments. This tumor, however, has not attained the degree of differentiation observed in trichoblastoma (1) another example of an immature cortical cell tumor. Squamous eddy-like or horn pearl-like foci of incomplete keratinization and large keratin-filled cysts were also present within the immature parenchyma, indicating that some immature cells were differentiating toward non-cortical cells, as found in the outer sheath. We would like to designate this tumor "rippled pattern trichomatricoma", a new entity.

Several monoclonal antibodies (MAB) have been produced using an eccrine carcinoma cell line as an immunogen. One such MAB, SKH1, reacted with both the secretory portion and coiled duct of the eccrine and with the secretory portion of apocrine gland. SKH1, however, did not react with myoepithelial cells, intradermal ducts of both types of sweat gland, or with other components of normal axillary skin including the epidermis and follicular apparatus. The reaction was strongest if the specimen was fixed with 80% methanol, and moderate on non-fixed or acid-alcohol-fixed specimens. Only weak reaction was obtained on cold acetone-fixed specimens, and reaction was negative with formalin-fixed, paraffin-embedded tissues. SKH1 reacted positively with the cytoskeleton of the eccrine carcinoma cell line, Colo-16 and MCF-7. Applied to pathological skin specimens, SKH1 reacted with the tumor cells of clear cell hidradenoma, syringocystadenoma papilliferum, and extramammary Paget's disease. SKH1 also reacted with the tumor cells of meta-static adenocarcinomas arising from lung, breast and ovary. SKH1 did not react with the majority of tumor cells of eccrine poroma, but reacted with single–layered cells lining narrow ductal lumina. SKH1 did not react with epithelial cells lining cystic or ductal lumina of syringoma, but reacted moderately with the amorphous keratin–like substance filling the lumina. Immunoblot analysis revealed that SKH1 recognizes a 40 Kd sweat gland-associated antigen, and can be an aid to identifying tumors arising from sweat gland structures.

Histologic, immunologic and electron microscopic studies were performed in a patient with transient acantholytic dermatosis which involved oral mucosa. Histologic and electron microscopic findings were almost identical in both cutaneous and mucous membrane lesions, and these were similar to pemphigus vulgaris; suprabasilar separation with acantolytic cells. Desmosome-desmosome complexes were separated without disruption of cell membranes and cytoplasmic structures were well-preserved without dyskeratosis. Lamina lucidia, however, was often separated in mucous membrane lesions, in contrast to the normal lamina lucida in cutaneous lesions of such cases or in pemphigus vulgaris. Direct and indirect immunofluorescence studies for pemphigus were repeatedly negative. This study shows that transient acantholytic dermatosis may involve mucous membrane and may resemble pemphigus vulgaris histologically and ultrastructurally except for the widened lamina lucida of the mucous membrane.

A 7-year-old Italian girl with juvenile colloid milium was studied with histological, immunohistochemical, and electron microscopic methods. This patient had a well-documented history of severe sunburn and developed the lesions on the face shortly afterward. Numerous apoptotic keratinocytes were observed in the lower epidermis. These cells began their degeneration with filamentous whorl formation (or filamentous degeneration) of tonofilaments. In the papillary dermis the colloid substance was resolved by the electron microscopy into either wavy, thin filaments derived from the epidermal keratinocytes or typical amyloid filaments. Many desmosomes and gap junctions were found in the colloid substance. Polyclonal antikeratin antibody (DAKO) was positive in the colloid substance, particularly in the parts close to the epidermis. These findings suggested that juvenile colloid milium is different from adult colloid milium despite clinical similarities and that the former belongs to the group of actinic amyloid K, i.e. amyloidoses due to actinic degeneration of keratinocyte and its keratin.

Electron dense membrane limited granules were observed in basal cells of the outer root sheath and in connective tissue sheath of the anagen sinus hair of mice. These granules were oval or round in configuration, and were 150--180 nm in size. They were considered to represent structures related to collagenolytic activity to accelerate elongation of anagen hair.

Five patients with mclanoacanthonia are reported. The skin lesions consisted of a single, round plaque measuring several centimeters in diameter. Histologic findings were characterized by formation within an acanthotic epidermis, of many islands of small basaloid cells and highly dendritic melanocytes. Electron microscopic examination of one lesion revealed a disturbance of melanin transfer from the highly dendritic melanocytes to the neighboring keratinoeytes.

Specimens from a patient with epidermolysis bullosa contained many elastic globes in the dermis. Ultrastructurally they were composed of (i) medium electron-dense amorphous substances, (ii) electron-dense round structures, and (iii) fine filaments. These various elements were seldom organized into typical normal elastic fiber and, therefore, it was difficult ultrastructurally to recognize them as such or components thereof. Immunohistochemically, elastic globes were strongly reactive with NKH-1, which stains elastic microfibrils, and antibody to serum amyloid P component (anti-SAP), which binds to elastic fiber microfibrils. However, elastic globes were negative with EKH-4 which recognizes 50 kd keratin of amyloid keratin and cytoid bodies. These findings suggested that elastic globes have a close immunologic profile to elastic fiber microfibrils, but not that of epidermal or epithelial keratin.

Tissues peripheral to well-developed papules of colloid milium were chosen for biopsy and electron microscopy examination. Evidence was presented that colloid is derived from elastic fibres through sequential degenerative changes. In the upper to middle dermis of the peripheral tissue, a number of abnormal masses in the vicinity of small colloid depositions were observed. Ultrastructurally, those abnormal masses were degenerating elastic fibres in which “electron-dense layers” of normal elastic fibre increased in amount, although their electron density diminished. Electron-light layers were gradually diminished in quantity. Degenerated elastic fibres finally became granulo-fibrillar and were indistinguishable from colloid. Many fibrils which closely resembled 10 nm tubular microfibrils of normal elastic fibre were observed in the granulo-fibrillar substance. Since one stage of the degeneration of elastic fibre which eventually leads to the formation of colloid milium was very similar to that of actinic elastosis, a direct role of sunlight in the formation of colloid milium is suggested.

A case of typical vibration-induced acrosclerosis was studied with the electron microscope. In addition to increased collagenization of the dermis, vascular wall and perivascular spaces, a severe vacuolization and an increased number of lysosomes in the vascular endothelia cells were observed. In many peripheral nerves, axonal degeneration, demyelination and an extensive collagenization of peri- and endoneurium were observed. These changes appeared to be the organic basis for sclerosis and neuropathies of this condition.

Normal epidermis of various sites of human body was examined by N-(7-dimethylamino-4-methyl-3-coumarinyl)maleimide (DACM) method for SH groups and SS linkages. The horny cells in the palm and sole showed a gradual occurrence of a SH membranous pattern, while those in other sites revealed an abrupt formation of the SH membranous pattern just above the granular layer. In the palm and sole epidermis the number of layers which exhibit membranous pattern of SH-positivity was thicker than that in the other other epidermis; the low- through mid-layers of horny cells in the former sites seemed to contain not only SS-positive but also SH-positive substance at cell peripheries. The DACM staining for SS linkages showed the presence of a granular fluorescence in the cytoplasm of the granular cells of the granular cells of the epidermis in the human palm and sole, but not in other sites. The granular cells in human lip displayed a granular fluorescence in the cytoplasm of the granular cells of the epidermis in the human palm and sole, but not in other sites. The granular cells in human lip displayed a granular fluorescence in the cytoplasm by either SH or SS DACM staining. All the SH- or SS-positive granular fluorescence was related to keratohyaline granules. These findings indicate that there may be some variations of the distribution pattern of the epidermal cellular proteins with SH and/or SS and a difference in chemical composition of keratohyaline granules between different anatomical sites of human body.

Several Moll's gland cysts from 4 different patients were studied with the light and electron microscopes. The cysts were lined with a combination of several different epithelia, such as completely keralinized epithelium, glycogen-rich, stratified squamous epithelium with incompletely keratinized luminal cells, sweat duct epithelium, and secretory cells. In one case in addition to the above components, secretory-type wall cells contained very large lamellar inclusions which were PAS positive and diastase resistant. It was concluded that Moll's gland cyst is composed of dilated duct of the Moll's gland and secretory segment; the proportion of each segment is variable but the portion showing ductal differentiation is usually predominant and typical secretory epithelium is not always seen.

Six examples of basal cell epithelium were compared to fetal and adult skin. Five parameters were used in this study: abnormally large aggregates of melanosomes in epithelial cells; the paucity of half-desmosomes; the increase of microfilaments in the cell periphery; clustered membrane-limited granules; and desmosome-like structures of stromal fibroblasts. All of these indicators were positive in both basal cell epithelioma and fetal hair follicle; but they were negative in both fetal and adult epidermis. Therefore, it was concluded that basal cell epithelioma seems to mimic fetal primary epithelial germ. Interestingly, stromal fibroblasts of basal cell epithelioma phagocytize collagen fibers, and membrane-limited granules were found both inside and outside the tumor cells facing the digested collagen stroma. In view of the collagenolytic activity of the homogenate of basal cell epithelioma, membrane-limited granules might represent zymogen granules for collagenases.

A 51-year-old immunosuppressed man presented with ulcerations of the abdominal wall. Biopsy of the ulcer margin was necessary for the diagnosis of cutaneous cryptococcosis. Since a variety of opportunistic organisms can present with non-specific cutaneous lesions, these infections must be ruled out by tissue diagnosis of all immunosuppressed patients. A review of 22 additional cases is included together with electron microscopic findings.

Blood vascular and lymphatic tumors were evaluated immunohistochemically by studying a spectrum of endothelial associated antigens. UEA-1 lectin reacted with the tumor cells of one patient with malignant angioendothelioma in the non-metastatic stage. However, when metastasis occurred, the binding sites of this lectin completely disappeared from the surface of the tumor cells in both original and metastatic lesions, suggesting the loss of blood group H antigen from the tumor cells could be used as an indicator of metastasis in this tumor. Reaction with anti-HLA-A, B, C, intense in normal blood vessels, remained intensely positive in pyogenic granuloma and Kaposi's sarcoma, whereas it did not react with normal lymphatics and lymphangioma. This indicates that anti-HLA-A, B, C is useful in differentiating blood vascular structures from lymphatic structures in both normal and pathological conditions. OKM5 reacted intensely with benign hyperplasias in pyogenic granuloma, while barely reacting with proliferating parts in Kaposi's sarcoma, suggesting the difference in staining patterns can be used to distinguish vascular proliferation or malignancy. Reaction with anti-Type IV collagen and anti-laminin was intense in normal blood vessels, pyogenic granuloma and Kaposi's sarcoma, whereas reaction with these antibodies in normal lymphatics was patchy and irregular in its thickness.

Serum amyloid P component (SAP) is present not only in all types of cutaneous amyloidosis, but also in the normal dermal elastic fibers as well as abnormal elastic fibers, such as elastotic degeneration of elastic fibers in actinic keratosis. It was previously postulated that the colloid substance in colloid milium is a final degeneration stage of actinic elastosis. In a lesion of colloid milium SAP was intensely positive with an indirect immunofluorescence method using rabbit antiserum to human SAP. Electron microscopy of the colloid lesion revealed components of normal elastic fibers as well as those of actinic elastoid as seen in actinic elastosis. It is concluded that the colloid substance derives, at least in major part, from elastic fibers through actinic degeneration.