A clinicopathological description of COVID-19-induced chilblains (COVID-toes) correlated with a published literature review.

BACKGROUND: The abundance of publications of COVID-19-induced chilblains has resulted in a confusing situation. METHODS: This is a prospective single-institution study from 15 March to 13 May 2020. Thirty-two patients received PCR nasopharyngeal swabs. Of these, 28 patients had a thoracic CT-scan, 31 patients had blood and urine examinations, 24 patients had skin biopsies including immunohistochemical and direct immunofluorescence studies, and four patients had electron microscopy. RESULTS: COVID-19-induced chilblains are clinically and histopathologically identical to chilblains from other causes. Although intravascular thrombi are sometimes observed, no patient had a systemic coagulopathy or severe clinical course. The exhaustive clinical, radiological, and laboratory work-up in this study ruled-out other primary and secondary causes. Electron microscopy revealed rare, probable viral particles whose core and spikes measured from 120 to 133 nm within endothelium and eccrine glands in two cases. CONCLUSION: This study provides further clinicopathologic evidence of COVID-19-related chilblains. Negative PCR and antibody tests do not rule-out infection. Chilblains represent a good prognosis, occurring later in the disease course. No systemic coagulopathy was identified in any patient. Patients presenting with acral lesions should be isolated, and chilblains should be distinguished from thrombotic lesions (livedo racemosa, retiform purpura, or ischemic acral necrosis).

Carcinoma mucinoso primario de piel / Primary mucinous skin carcinoma

El adenocarcinoma mucinoso primario de piel es una neoplasia anexial, maligna e infrecuente, que afecta principalmente a hombres en una relación 2:1 con respecto a las mujeres. Presenta mayor incidencia entre la sexta y séptima década de la vida, y se manifiesta como un tumor único, asintomático, de tamaño variable. La localización más frecuente es la región periorbitaria y el cuero cabelludo. Se comunica el caso de una paciente de 92 años, con diagnóstico de carcinoma mucinoso primario de piel, sin evidencia de enfermedad sistémica ni recurrencia local al año de la resección por cirugía micrográfica de Mohs. Describimos sus principales características clínicas, dermatoscópicas y hallazgos histopatológicos. (AU)

Primary mucinous adenocarcinoma of the skin is an adnexal, malignant, and infrequent neoplasm that mainly affects men with a 2: 1 ratio, with respect to women. It presents higher incidence between the sixth and seventh decade of life, and manifests as a single tumor, asymptomatic, of variable size. The most frequent location is the periorbital region and scalp. We report the case of a 92-year-old patient with a diagnosis of primary mucinous skin carcinoma, without evidence of systemic disease or local recurrence one year after resection by Mohs micrographic surgery. We describe its main clinical features, dermatoscopic and histopathological findings. (AU)

Expression of S100A2 and S100P in human eccrine sweat glands and their application in differentiating secretory coil-like from duct-like structures in the 3D reconstituted eccrine sweat spheroids.

Secretory coils and ducts are two components of eccrine sweat glands with different structures and functions. In our previous study, we combined keratins and α-SMA to distinguish between secretory coils and ducts. However, the key deficiency of the method was that none of the antibodies used was specific for ducts. In this study, we first examined the co-localization of K5/K7, α-SMA/K14, K7/S100P and α-SMA/S100A2 by double-immunofluorescence staining to confirm the localization of S100P and S100A2 in native human eccrine sweat glands, and second we identified secretory coil-like and duct-like structures in the 3D reconstituted eccrine sweat gland spheroids by double-immunofluorescence staining for K7/S100P and α-SMA/S100A2. In native human eccrine sweat glands, S100A2 immunoreactivity was confined to the outer layer and S100P to the inner layer of the duct. In 12-week Matrigel plugs containing eccrine sweat gland cells, double-immunofluorescence staining for K7/S100P and α-SMA/S100A2 could easily distinguish duct-like structures from secretory coil-like structures. We conclude that S100A2 and S100P can be used as specific duct markers in eccrine sweat glands, and combined use of S100P or S100A2 with keratins enables easy to distinction between secretory coils and ducts.

Cytochemistry of sialoglycoconjugates, lysozyme, and ß-defensin in eccrine glands of porcine snout skin as studied by electron microscopy.

In most mammals except for humanoid primates, eccrine glands are confined to the skin of a series of specific body regions. Sialic acids and antimicrobial substances exhibit various functional properties and serve as a component of nonspecific defense against micro-organisms, respectively. In this study, the distribution of these moieties was studied by electron microscopic histochemical methods. The eccrine glandular acini consisted of two types of dark cells as well as clear cells. The secretory granules and Golgi apparatus of both types of dark cells contained sialic acid residues linked to α2-6Gal/GalNAc. On the other hand, sialoglycoconjugates with Siα2-3Galß1-4GlcNAc sequence were confined to those of the Type II dark cells. In addition, lysozyme and ß-defensin were mainly detected in the secretory granules of the Type II dark cells. These secretory products may create a defensive barrier against microbial invasion and play an essential role in preservation of the integrity of porcine snout skin as a sensory organ.

Neuronal ceroid lipofuscinosis diagnosed via skin biopsy.

We aim to report that skin biopsy, a non-invasive test by neurological standards, may lead to a diagnosis. A 4-year-old male presented with a 2-year history of epilepsy and progressive developmental regression. The patient had a mildly elevated ammonia level; however, evaluation for the accumulation of excess serum amino acids and evaluation of urine for organic acids was negative. MRI revealed cerebral atrophy, and an electroencephalogram demonstrated multifocal sharp and slow waves. Due to the progressive degenerative neurologic presentation, a neurologic storage disease was favored. An axillary skin biopsy was performed, revealing eosinophilic intra-cytoplasmic inclusions within the eccrine glands. A periodic acid-Schiff stain also highlighted these inclusions. Electron microscopic studies demonstrated characteristic multiple membrane-bound inclusions within the eccrine epithelial cells, containing curvilinear inclusion material characteristic of neuronal ceroid lipofuscinosis. The clinical, histological, electron microscopic and enzymatic studies were diagnostic of late-infantile onset neuronal ceroid lipofuscinosis.

Immunohistochemical and electron microscopic studies of Langerhans cells in a case of multiple eccrine spiradenomas.

Multiple eccrine spiradenomas are rare. In the present study, a detailed investigation of eccrine spiradenoma was performed, focusing in particular on the presence of Langerhans cells (LCs) in the tumor, and their immunohistochemical and ultrastructural characterization. The patient was a woman in her mid-forties who underwent resection of two tumors of the head that were 2.0 and 0.7 cm in size. They were diagnosed as eccrine spiradenoma and were composed of small and large tumor cells with a dense fibrous capsule in the dermis. Immunohistochemically, staining by antibodies to cytokeratins (AE1/AE3, CAM5.2) and CK 5/6 was diffusely positive in all tumor cells, although not in intermingled LCs, which harbored interdigitated nuclei. The cytoplasm of LCs was positive for S-100 protein and CD1a, and their nuclei were also occasionally positive for S-100 protein. Antibody to epithelial membrane antigen was positive for the surface of both intracytoplasmic and true glandular lumina. Fine structural examination revealed the presence of LCs among the tumor cells, extending fine irregular processes among the tumor cells. Birbeck granules were clearly demonstrated in the cytoplasm of LCs. Other fine structural findings included intracytoplasmic lumina with microvilli on their surfaces in some tumor cells. In these examinations of eccrine spiradenoma, LCs, approximately 15/HPF in the tumor, were distinctly detected even at light microscopic level as negative for various types of cytokeratin stains, although they were positive for S-100 protein and CD1a, whereas on ultrastructural examination Birbeck granules were demonstrated in their cytoplasm. Determination of the significance of these LCs in eccrine spiradenoma requires further investigation of a larger number of cases.

Ultracytochemical demonstration of glycoproteins in the eccrine glands of the digital pads of the North American raccoon (Procyon lotor).

In the eccrine glands of the digital pads of the North American raccoon (Procyon lotor), ultrastructural localization of glycoproteins with various saccharide residues was studied using preferably lectin cytochemical methods. Secretory granules observed in the dark cells exhibited glycoproteins with different terminal sugars (alpha-D-mannose, beta-D-galactose, beta-N-acetyl-D-glucosamine and sialic acid). The cytoplasm of the clear cells contained numerous glycogen particles. Several sugars were also detectable in the surface coat of the plasma membrane of the secretory cells. The results obtained could be helpful in understanding secretion production and cell related secretion functions of the eccrine glands of the raccoon digital foot pads.

Ultrastructure of the apical glandular region of the scolex of Proteocephalus torulosus (Cestoda: Proteocephalidae).

In the apical glandular region of the adult Proteocephalus torulosus (Batsch, 1786), two types of eccrine gland cells are present. The first type of unicellular gland produces large electron-dense granules of various sizes. The second type contains small electron-dense granules. Most cells form glands with large granules; glands with small granules are infrequent. The secretion of both types of gland cells is concentrated in the apical parts of the cyton and in the ducts opening to the exterior. On the scolex of P. torulosus, there are regional structural differences of the microthrix border. The apical glandular region bears filamentous microtriches only. On the remaining frontal part, surrounding the glandular region, there are blade-like and filamentous microtriches. The lateral parts of the scolex and suckers bear blade-like microtriches. Possible functions of both types of gland cells and different parts of the scolex microthrix border are discussed. The unique structure of the frontal part of the scolex of P. torulosus and its differences from Proteocephalus macrocephalus, P. longicollis and P. percae correlate well with the putative basal phylogenetic position of P. torulosus among European species of Proteocephalus.

Cutaneous eccrine glands of the foot pads of the small Madagascan tenrec ( Echinops telfairi, Insectivora, Tenrecidae): skin glands in a primitive mammal.

In order to find correlations between skin gland morphology and specific ethological features, the cutaneous glands of the foot pads of the primitive mammal the Madagascan tenrec, Echinops telfairi, were studied by histological and various histochemical methods as well as by electron microscopy. In the foot pads specific eccrine skin glands occurred consisting of coiled ducts and tubular secretory portions, the lumina of which were considerably wider than in primate sweat glands. The secretory tubules were composed of branched myoepithelial cells and glandular cells. The latter contained abundant mitochondria, large amounts of glycogen particles and few secretory granules as well as individual heterolysosomes and myelin bodies. The lateral cell membrane was marked by extensive interdigitations. The apical membranes of all glandular cells contained proteoglycans with sulfated and carboxylated groups containing N-acetyl-glucosamine, N-acetyl-galactosamine, galactose and mannose. The expression pattern of cytokeratins of the glandular epithelium was variable and showed similarities to that of the human eccrine glands. Tubulin, vinculin and actin were expressed in the glandular epithelium. The secretory cells showed positive reactions with antibodies against antimicrobial peptides and IgA. A positive reaction was observed with antibodies against the androgen receptor. The PCNA and TUNEL reactions indicated that the tubular skin glands of Echinops are made up of a slowly renewing tissue. We conclude that the glands fulfill several functions: production of a fluid-rich secretory product, which may prevent slipping of the foot pads on the substrate during running or climbing, secretion of antimicrobial peptides and proteins, and playing a role in thermoregulation.

PACAP activated adenylate cyclase in human sweat glands. An ultracytochemical study.

The ultracytochemical localization of adenylate cyclase (AC) was studied after stimulation with pituitary adenylate cyclase activating peptide (PACAP) in human sweat glands. PACAP stimulated AC in both eccrine and apocrine glands. In the secretory cells, enzymatic activity was associated with membranes involved in the secretory mechanism. In both glands, the cells of the excretory duct and myoepithelial cells presented AC activity. These localizations of enzymatic activity suggest a role for PACAP in regulating glandular secretion.

Structure and function of human sweat glands studied with histochemistry and cytochemistry.

The basic structure and the physiological function of human sweat glands were reviewed. Histochemical and cytochemical techniques greatly contributed the elucidation of the ionic mechanism of sweat secretion. X-ray microanalysis using freeze-dried cryosections clarified the level of Na, K, and Cl in each secretory cell of the human sweat gland. Enzyme cytochemistry, immunohistochemistry and autoradiography elucidated the localization of Na,K-ATPase. These data supported the idea that human eccrine sweat is produced by the model of N-K-2Cl cotransport. Cationic colloidal gold localizes anionic sites on histological sections. Human eccrine and apocrine sweat glands showed completely different localization and enzyme sensitivity of anionic sites studied with cationic gold. Human sweat glands have many immunohistochemical markers. Some of them are specific to apocrine sweat glands, although many of them stain both eccrine and apocrine sweat glands. Histochemical techniques, especially immunohistochemistry using a confocal laser scanning microscope and in situ hybridization, will further clarify the relationship of the structure and function in human sweat glands.

Cutaneous eccrine glands of the foot pads of the rock hyrax (Procavia capensis, Hyracoidea, Mammalia).

In order to find correlations between skin gland morphology and specific ethological features, the cutaneous glands of the foot pads of Procavia capensis were studied by histological and various histochemical methods and by electron microscopy. In the foot pads, abundant specific eccrine skin glands occur, which consist of coiled tubular secretory portions and coiled ducts. The wall of the secretory part is composed of cuboidal glandular cells and myoepithelial cells. Among the glandular cells two types occur: clear and dark cells. Clear cells have numerous mitochondria and form a basal labyrinth, indicating fluid transport. Dark cells, which stain strongly with periodic acid-Schiff, contain a highly developed perinuclear Golgi apparatus, large amounts of rough endoplasmic reticulum and many secretory granules indicating production of glycoproteins. Cytokeratin (CK) 19 was found in secretory compartments and ducts, CK14 only in duct cells. Single cells of the secretory coils and ducts may be stained with antibodies against antimicrobial peptides. Some glandular cells contain proliferating cell nuclear antigen-positive nuclei especially in the ducts indicating an increased cell proliferation. Terminal transferase (TdT)-mediated d-UTP nick-end labeling-positive nuclei can be detected predominantly in the secretory coils and rarely in the transitional portions between ducts and end pieces. We suppose that proliferating cells migrate from the ducts to the secretory coils. The secretory product of the eccrine cutaneous glands seems to improve the traction between the foot pads of these animals and the steep and smooth rock formations among which they live.

[Primary signet ring cell carcinoma of the eccrine sweat gland in the eyelid. Immunohistochemical and ultrastructural study of a case]. / Adénocarcinome sudoral primitif de la paupière de type eccrine à cellules en bague à chaton.

We report a case of a 45-year-old woman who exhibited a primitive eccrine sweat gland carcinoma of the eyelid. Histological study showed cellular proliferation with an Indian file pattern and some signet ring cells with sialomucin secretion. Immunohistochemical study demonstrated these cells to be positive with the anticytokeratin, anti-EMA, anti-HMFG, antiestrogen receptor and antiprogesterone receptor antibodies. Ultrastructural study showed intracytoplasmic vacuoles with numerous microvilli at the apical side. Differential diagnosis with a metastasis from a mammary adenocarcinoma is difficult and a complete staging is necessary to confirm the primitive origin of the tumor. The behavior of this tumor is marked by locoregional recurrence.

Ultrastructure of the hyperhidrotic eccrine sweat gland.

BACKGROUND: Hyperhidrosis is the secretion of inappropriately large amounts of sweat by eccrine glands; it can be very debilitating. Little is known of the causes of primary hyperhidrosis. OBJECTIVES: To determine whether the glands exhibit any structural abnormality in primary hyperhidrosis. METHODS: Skin biopsies were obtained from the axilla (n = 6) or neck (n = 2) of individuals aged 26-62 years with primary hyperhidrosis and from five age- and sex-matched normal individuals, with informed consent and ethical committee approval. Samples were prepared by standard methods for light and electron microscopic examination. RESULTS: All characteristics observed in the hyperhidrotic specimens were consistent with the changes seen in normal glands following strong activation: degranulation of the granular (dark) cells, dilatation of the basolateral infoldings and the canaliculi of the non-granular (clear) cells, contraction of the myoepithelial cells and thickening of the basal lamina, and presence of cellular debris including lipid droplets in the gland lumen. Pathological changes were not observed. CONCLUSIONS: The present finding of the absence of structural defects in the glands indicates that future studies should concentrate on the investigation of neurohumoral or secretory cell metabolic abnormalities.

Dystrophic scrotal calcinosis originating from benign eccrine epithelial cysts.

Scrotal calcinosis has been classified as a form of idiopathic calcinosis cutis. However, the pathogenesis of the calcified nodules has not been fully elucidated: it is still unclear whether the condition is truly idiopathic, or the result of breakdown of calcified epithelial cysts. We describe a 29-year-old Japanese patient with scrotal calcinosis originating from epithelial cysts. Light microscopy revealed a large epithelial cyst containing von Kossa-positive material and several small dilated ductal structures beside the cyst. The epithelia of the cyst and ductal structures were connected, showing similar eccrine duct differentiation on immunohistochemical staining and electron microscopy. In the cyst lumen, calcium was present as needle-shaped crystals. The pathogenetic mechanism of calcium deposition seemed to be due to excessive production and discharge of matrical debris and sulphated mucopolysaccharides, which derived from luminal cells, and their accumulation in the lumina.

Ultrastructure studies of Proteocephalus longicollis (Cestoda, Proteocephalidea): transmission electron microscopy of scolex glands.

The ultrastructure of two types of secretory glands in the scolex of preadults of Proteocephalus longicollis is described for the first time in the present report. The gland cells contain extensive cisternae of granular endoplasmic reticulum and Golgi complexes, which participate in the production of secretory globules. Type I scolex glands produce electron-dense globules of various size. The secretory globules enter the secretory canal, openings of which were not observed in the preadults. The secretory product of type I was found at the inner sucker surface and in the tegument of the sucker edges. In addition, electron-dense globules in adult worms are secreted via an eccrine mechanism. Type II scolex glands are characterized by secretory globules of lower electron density and occur mainly in preadults. The electron-lucent, membrane-bound secretory globules are transported via microtubule-lined ducts opening to the exterior at the tegumental surface. Secretory globules of type II are released by an eccrine process.

The ultrastructural characteristics of eccrine sweat glands in a Fabry disease patient with hypohidrosis.

As an investigation of the pathogenetic mechanism of diminished sweating in Fabry disease, an electron microscopy ultrastructural study was conducted on specimens of eccrine sweat glands from a typical patient with Fabry disease who had hypohidrosis, a low skin moisture content, and diminished thermoregulation ability. Numerous characteristic cytoplasmic inclusions were observed in the eccrine sweat glands, the lamellar pattern of which was considerably variable in various types of gland cells. Large vacuolar inclusions predominated in clear cells of secretory coil; lesser vacuoles were also seen in the coiled duct, and the basal cells of the straight duct toward the coiled duct displayed mulberry-like figures. There were some clear cells showing cell damage and necrosis in the secretory coil. Lamellated inclusions were noted in the unmyelinated axons innervating the eccrine sweat glands. The small blood vessels around the eccrine glands were narrowed by swollen endothelial cells with heavy inclusions. These intracytoplasmic deposits may be responsible for the decreased sweating ability in Fabry disease. The factors related to hypohidrosis are also discussed.

Papillary eccrine adenoma: an ultrastructural and immunohistochemical study.

A 45-year-old African American man presented with a small, solitary, nonulcerated cutaneous lesion of the right thigh of many years duration, which was excised. Light microscopically, the lesion consisted of an oval, well-circumscribed, intradermal proliferation of tubules, which were often dilated and lined by a double layer of tumor cells with conspicuous intraluminal papillations. Ultrastructurally, there was evidence of both intradermal eccrine duct and eccrine secretory coil differentiation. Although the majority of tumor cells resembled cells of the intradermal eccrine duct, occasional myoepithelial tumor cells and rare tumor cells having secretory granules and resembling dark mucous cells were indicative of eccrine secretory coil differentiation. The positive immunohistochemical staining for S-100 protein, CEA, EMA, and vimentin supported these ultrastructural findings.

Denervation of eccrine glands in patients with familial amyloidotic polyneuropathy type I.

OBJECTIVE: To study the alterations in the structure and innervation of eccrine glands in familial amyloidotic polyneuropathy (FAP) type I with Val 30 Met transthyretin mutation. BACKGROUND: Anhidrosis of the distal lower limbs is a prominent feature of FAP type I. METHODS: Qualitative and morphometric study of amyloid deposition, eccrine glands, and their innervation in nine patients with FAP type I (duration of sensory symptoms, 8.4 +/- 3.9 years [mean +/- SD]; range, 3 to 15 years) and seven control subjects. RESULTS: On light microscopy, the endoneurium of cutaneous nerve fascicles had no definite amyloid deposition. Amyloid deposition was observed around eccrine glands in seven of nine patients. On electron microscopy, no focal destruction and degeneration of eccrine glands or ducts and of Schwann cell processes with or without nerve terminals or unmyelinated axons were observed in relation to adjacent amyloid deposition. Secretory vacuoles and granules of dark cells were markedly decreased in some secretory coils. Nerve terminals and unmyelinated axons of eccrine glands were considerably fewer in patients than in control subjects, and denervation was prominent in all patients. A few nerve terminals and unmyelinated axons of eccrine glands were present in patients who had experienced sensory symptoms for 3, 5, and 6 years, but were absent in patients with sensory symptoms for more than 7 years. CONCLUSIONS: Eccrine glands are markedly to totally denervated in patients with FAP type I and chronic sensory symptoms. The extent of denervation indicates the severity of autonomic denervation and therefore may suggest the timing of liver transplantation.