Langerhans Granules Research Articles

A patient with diabetes insipidus and periorbital swellings; Erdheim–Chester disease

Erdheim–Chester disease is a rare multisystem disease in which a progressive xanthogranulomatous infiltration of several tissues can be seen. We describe a woman, known to have diabetes insipidus for ten years, with periorbital, retroperitoneal, mediastinal, axillar and inguinal involvement. On histological examination a granulomatous infiltration of fatty tissue and striated muscle was seen, consisting of Touton giant cells, histiocytes with foamy cytoplasm and lymphocytes. Immunohistochemical staining with CD-1a and S-100 was negative and on electron microscopy no Langerhans granules were seen. These findings led to the diagnosis of Erdheim–Chester disease. She had a good response on steroids. Because of some similar clinical features of Langerhans cell histiocytosis and Erdheim–Chester disease, a histiocyte disorder seems the most probable cause.

A possible role for Langerhans cells in the removal of melanin from early catagen hair follicles.

Hair pigmentation is coupled to the hair follicle growth cycle. A common feature of catagen is the translocation of melanin from the matrix to the dermal papilla of the hair follicle. However, the mechanism whereby this pigment, not incorporated into the hair shaft, is removed from the hair bulb during early catagen is poorly understood. Routine ultrastructural examination of four normal scalp specimens revealed a rare hair follicle in early catagen. Close study of the hair bulb of this catagen follicle revealed a Langerhans cell in the process of transferring pigment from the matrix to the dermal papilla. This cell also contained numerous characteristic Langerhans granules (LG) (also known as Birbeck granules). Interestingly, these granules were intimately associated with melanosomes: so intimate, in fact, that melanosomes appeared to have been endocytosed by LG. This unique demonstration of removal of hair follicle melanin by Langerhans cells during early catagen and of pigment uptake by Langerhans cells by endocytosis into LG, suggests one way by which 'unused' pigment can be removed from the hair follicle during catagen.

Granuloma Faciale: An Ultrastructural Study

Granuloma faciale is an uncommon process that can easily be confused with other skin diseases. To avoid incorrect treatment, correct diagnosis is of primary importance. A diagnosis of granuloma faciale can be made by a microscopic study of the dense granulomatous infiltrate in the reticular dermis with abundant polynuclear eosinophils and by an ultrastructural study of the eosinophils, which show characteristic alterations in their cytoplasmatic granules. The absence of Langerhans granules differentiates granuloma faciale from histiocytosis X.

Langerhans cells in the larynx and the hypopharynx.

Langerhans cells are important in the human immune system as a part of the dendritic cell system. This study was carried out to demonstrate the presence of Langerhans cells and their distribution in normal human larynx and hypopharynx, by light (S-100 polyclonal antibody) and transmission electron microscopy. The results are summarized as follows: 1) Langerhans cells with cytoplasmic granules (Langerhans granules or Birbeck's granules) were situated in the suprabasal region of the squamous epithelium in the larynx and the hypopharynx. 2) They distributed in the membranous portion of the vocal folds, epiglottis, aryepiglottic folds, arytenoid regions and interarytenoid notch of the larynx. The cells surrounded the vestibule and glottis of the larynx. 3) They distributed in the postcricoid area, piriform sinus and posterior pharyngeal wall of the hypopharynx. The cells were situated above the entrance of esophagus. 4) The cells were suggested to be a factor of immune response at the entrance of trachea and esophagus.

Erdheim-chester disease: A case report with immunohistochemical and biochemical examination

This report describes a 47-year-old man with Erdheim-Chester disease (EC), the second case reported in Japan. The patient complained of knee pain, and the roentgenogram of the bilateral legs revealed symmetric osteolytic lesions with sclerosis of the metaphyseal regions of the long bones. Histological examination of the biopsy specimen showed a xanthogranulomatous lesion consisting of aggregations of foamy macrophages and Touton-type giant cells. Immunohistochemical study of the foamy cells in the lesion showed positive reaction to anti-Kp-1, anti-S-100 α, β, anti-neuron-specific enolase (NSE), anti-α-l-antichymotrypsin, anti-α-l-antitrypsin, and anti-lysozyme antibodies. Electron microscopy showed many lipid droplets in the cytoplasm, but no Langerhans granules. These results suggested that the disease was part of the spectrum of histiocytosis but was different from Langerhans cell histiocytosis. Biochemical analysis of material extracted from a lesion showed the predominance of cholesterol ester. The disease progressed to central diabetes insipidus, and the involvement of multiple organs was indicated by a magnetic resonance image.

Primary Cutaneous Langerhans Cell Histiocytosis in an Adult

An unusual adult case of Langerhans cell histiocytosis is presented. The case initially mimicked granuloma annulare, both clinically and histologically. The patient subsequently had development of extensive cutaneous involvement that pathologically revealed a diffuse infiltrate of CD1-positive histiocytic cells containing Langerhans granules. Extensive investigations failed to detect systemic involvement. The patient's cutaneous eruption did not respond to various therapeutic interventions, including phototherapy with oral psoralen with long-wave UV radiation in the A range (PUVA) and systemic vinblastine sulfate. Marked but temporary clinical and histologic improvement was achieved with total body electron beam radiotherapy. The nosology of this case is discussed in the context of the various histiocytic proliferative disorders.

Deep Juvenile Xanthogranuloma

Juvenile xanthogranuloma occurring in soft tissue is rare and has received little attention. This report describes cases of deep juvenile xanthogranuloma occurring in the soft tissues of three children. Each tumor was a solitary lesion that arose, respectively, in the superficial skeletal muscles of an 8-month-old girl, the subcutis of the scalp of a 3-month-old boy, and the subcutis of the forehead of a 10-year-old girl. Two lesions were grossly firm, tan-yellow, and homogeneous. Histologically, the subcutaneous lesions were relatively circumscribed; the third lesion infiltrated muscle and contained widely separated skeletal muscle fibers. All lesions showed sheets of uniform amphophilic or acidophilic cells with occasional eosinophils and rare Touton giant cells. In two cases and in cutaneous controls, positive immunoperoxidase stains (HAM-56, HHF-35, and vimentin) supported macrophagic-myofibroblastic differentiation. S-100 protein, MAC-387, and factor XIIIa were negative. Electron microscopy in one case also supported macrophagic-myofibroblastic differentiation. Langerhans granules were absent. Follow-up of 7, 6, and 5 years indicated no recurrences. The differential diagnosis includes deep fibrous histiocytoma and cellular subcutaneous neural tumors.

Urticating histiocytosis: A mast cell-rich variant of histiocytosis X

Histiocytosis X and mastocytosis are proliferative processes that may have similar cutaneous manifestations. However, a positive Darier's sign (urtication on stroking of the lesion) is thought to reliably distinguish between these two diseases. We recently studied a 13-year-old girl with a 2-year history of extensive skin lesions and a positive Darier's sign. Routine histopathologic studies revealed a polymorphous cutaneous infiltrate composed of histiocytes, mast cells, eosinophils, and lymphoid cells. Electron microscopic studies demonstrated Langerhans granules in some of the histiocytes, and immunologic studies of frozen tissue showed that a significant subpopulation of the histiocytes marked as Langerhans cells. Giemsa staining of specimens from eight other cases of cutaneous histiocytosis X from our files revealed mast cells in all of the lesions, although none showed the abundance of mast cells present in the case with urtication. Our studies emphasize the often polymorphous nature of the cell population in cutaneous histiocytosis X and demonstrate that confusing clinical findings can result when the mast cell population in histiocytosis X produces urtication.

Juvenile xanthogranuloma with central nervous system lesions

We describe two boys in whom extensive normolipemic cutaneous papulonodular xanthomatous lesions developed and disabling central nervous system disease later developed. Histologically, lesional skin from each patient was consistent with juvenile xanthogranuloma. Electron microscopic studies in each case failed to reveal Langerhans (Birbeck) granules. Results of S-100 protein studies done with the peroxidase-immunoperoxidase technic were negative in each case. Radiation therapy and systemic corticosteroids have been partially successful in controlling the cerebellar ataxia experienced by one of the patients. The other patient had progressive central nervous system disease and died 8 years after the onset of his skin lesions despite radiation therapy and systemic chemotherapy. We believe that these cases are examples of normolipemic, xanthomatous, non-X histiocytosis with features of juvenile xanthogranuloma and aggressive central nervous system disease.

Cutaneous non-X histiocytosis: Clinical and histologic features and response to dermabrasion

A 22-year-old man presented with a progressive cutaneous eruption consisting of reddish-yellow papules and plaques on his face, which was histopathologically characteristic of a non-X histiocytosis. No systemic involvement was present. Monoclonal antibody staining of the tissue infiltrate was strongly positive for only OKT6. On electron microscopy, Langerhans (Birbeck) granules were not found. Four years of conservative treatment was unsuccessful. Spontaneous involution did not occur. Dermabrasion not only produced excellent cosmetic results, but on rebiopsy the histiocytic infiltrate was absent. There has been no recurrence in treated areas after 18 months.

Letterer-Siwe disease in an octogenarian

The case of an 81-year-old woman suffering for about 1 year from a typical form of Letterer-Siwe disease (LSD) is reported. The only important systemic involvement was hepatosplenomegaly. The patient was treated with steroids and vinblastine and then with thymopoietin pentapeptide. This last drug proved useful for decreasing the dose of steroid and thus for checking the appearance of new skin lesions. The ultrastructural investigations, carried out before and after vinblastine, showed the presence in some histiocytosis X cells (HXC) of coated Birbeck granules (BG). Immunoelectron microscopy showed about 90% of HXC to be OKT6+ and the OKT6 labeling of these cells to be similar to that of the Langerhans cells of normal skin. Five percent of OKT6+ cells apparently contained no Langerhans granules.

A second look at intraepithelial Langerhans cells in mycosis fungoides and related disorders

Skin biopsies of patients with small and large plaque parapsoriasis, premycotic lesions and mycosis fungoides in different stages were examined. Special attention was paid to the relationships between Langerhans cells (LC) and the neighbouring keratinocytes and lymphocytes. At the contact areas of LC and keratinocytes as well as LC and lymphocytes, particular cell membrane phenomena were observed. Aggregations of Langerhans granules and fusions of granules with LC plasma membranes were found exclusively at LC-keratinocyte interfaces. At LC-lymphocyte contact zones cell membrane appositions were seen. In all cases investigated, virus-like particles were mainly found in LC and indeterminate cells (IDC). In 3 cases lymphocytes also contained these particles. It was of particular interest that virus-like particles were observed in skin specimens of all diseases investigated. Discrimination of these particles from other cellular organelles - especially lysosomes - was difficult, however. The significance of our findings, particularly regarding to the supposed virus aetiology of cutaneous T cell lymphomas, is discussed.

Langerhans cells in normal human skin capillaries

Cells with Langerhans granules are reported for the first time in normal human skin capillaries.

Functional anatomy of lymph nodes. II. Peripheral lymph-borne mononuclear cells.

In the rabbit a number of large mononuclear cells with ruffled surface membranes travel from the skin and superficial tissues of the leg, via the lymphatics, to the popliteal lymph node: they constitute 40-50% of the total cell population in the afferent lymph. About 10% of these cells are actively phagocytic when tested in vitro and about 3% are found to contain Langerhans granules. After isotopic labelling the majority of lymph-borne mononuclear cells can be detected within the regional node for at least 24 hours; most being located in the paracortex and a few in the interfollicular cortex. It is proposed that these cells, including those containing Langerhans granules, belong to the "mononuclear phagocyte system." Possible functions of these lymph-borne cells are discussed with particular reference to antigen transport.

Langerhans cells and interdigitating reticulum cells in the thymus-dependent region in human dermatopathic lymphadenitis.

14 cases of dermatopathic lymphadenitis were studied by light and electron microscopy. In two instances the ATP-ase reaction was applied to lymphoid tissue. The main morphologic feature of dermatopathic lymphadenitis is an extreme enlargement of the thymus-dependent area which is due to a large number of closely connected, interdigitating reticulum cells (IDC). Enzyme-histochemically IDC are ATPase positive. In all systematically studied cases Langerhans cells are found in the paracortex. They may also be present in the sinuses and the neighbouring lymph node parenchyma. Like IDC, Langerhans cells have an irregularly shaped nucleus, numerous cytoplasmic processes as well as invaginations; in the paracortical area they show intimate connections with each other or with IDC. Frequently they can be differentiated from IDC only by the presence of Langerhans granules. The close topographic apposition to T-lymphocytes typical of IDC is also true of Langerhans cells.

Histiocytosis X of the Skin in an Elderly Man

A diffuse truncal cutaneous eruption of six months' duration in a 76-year-old man is described. Light and electron microscopy revealed infiltration of the papillary dermis and overlying epidermis by histiocytic cells containing Langerhans granules, findings characteristic of histiocytosis X. The Langerhans cell as a probable cell of origin and unifying feature for the subtypes of histiocytosis X is discussed. It is suggested that with increased awareness of the variability of histiocytosis X, atypical presentations will be identified more frequently.

Electron microscopical study of psoriasis pustulosa.

Five cases of psoriasis pustulosa were examined by electron microscopy. The main features within the dermis were dilated capillaries filled with polymorphonuclear leukocytes and red cells. Neutrophils passed out of the vessels through the gaps and fenestrations and migrated towards the epidermis throughout the distinctly edematous corium. Lymphatic vessels could be found. Histiocytes containing Langerhans granules were observed in the dermis and epidermis. The morphological changes of the epidermis depented on the place examined and were most evident near fully developed pustules in the upper layers. The presence of previously described morphological findings could be confirmed. Perinuclear cytolysis and other changes in the keratinocytes, however, seem to be secondary, resulting from edema and accumulation of neutrophils within the epidermis. Immunological phenomenona may be responsible for the latter event.

Freeze-fracture of langerhans granules. A comparative study

A comparative study of freeze-fracture replicas and thin sections of Langerhans granules has proved that the effects of conventional tissue processing on the inner structure of the granule are negligible, and the study has confirmed the validity of the previously proposed tridimensional models. The paracrystalline quality of the substance contained between the limiting membranes of the disc-shaped area of the granules seems to suggest it protein nature. In replicas, no particle organizations attributable to intercellular junctions were observed on the plasma membranes of Langerhans cells.

The fine structure and cell kinetics of mouse epidermis after wounding.

A variable amount of cornified tissue removed from mouse dorsal epidermis results in stimulation of the entire basal layer. Stimulation does not appear to be dependent on damage to an indiviaual epidermal proliferative unit (EPU). The immediate reaction to wounding is a rapid movement of cells from the basal layer to the differentiating compartment resulting in depopulation of the basal layer, which is followed by a burst in DNA-synthetic activity. The result of the increased transit of cells through the epidermis is that various aspects of keratinization can appear abnormal. The Langerhans cells show several changes, often appearing suprabasal and becoming smaller, rounded cells with a less-clear cytoplasm and fewer granules. The initial migratory reaction results in a largely normal epidermis on the third day. This reaction is followed by a transient hyperplasia which reaches its peak on the sixth to seventh day and gradually returns to normal by the fourteenth to fifteenth day. The hyperplasia is characterized by a loss of the ordered stacking of cornified cells which become shorter and thicker than normal. There is a return to the stacked state beginning on the tenth day. The Langerhans frequency is apparently at its lowest on days 6-7 when the proliferation levels are at their maximum. An inverse relationship appears to exist between relative Langerhans cell frequency and cell proliferation rate. The data suggest that the frequency of Langerhans granules also changes during the course of the hyperplasia, peak levels being observed just before the decline in proliferative activity.

Dense bodies and langerhans granules after application of podophyllum resin

The application of an alcoholic solution of podophyllum resin at concentrations above 10% for seven hours on guinea-pig udders increases the number of dense intracytoplasmic bodies in the Langerhans cells localized in the epidermis. A close relationship can be established between these inclusions and the typical Langerhans granules in view of the numerous intermediate forms with features of one or the other. Serial sections of these structures confirm the irregularity not only of the lysosome-like bodies but also of the Langerhans granules, which may be fusiform or oblong or even present two vesicular dilatations, one at each end of the rod.