Which histologic findings are characteristic of Langerhans cell histiocytosis (LCH)?

Updated: Jun 12, 2020
  • Author: Christopher R Shea, MD; Chief Editor: William D James, MD  more...
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The histologic picture unifies the varied presentations of Langerhans cell histiocytosis (LCH), which are influenced by the location and age of the lesions. Although lesions typically appear granulomatous, with a reactive background of macrophages, eosinophils, multinucleated giant cells, and T-cells, the key to diagnosis is to identify the pathologic Langerhans cells. [52, 60] The latter cell resembles the normal Langerhans cell of the skin, except that it is not dendritic. It consists of a large, ovoid, mononuclear cell that is 15-25 µm in diameter, with a folded nucleus, a discrete nucleolus, and a moderate amount of slightly eosinophilic homogeneous cytoplasm. When the indentation of the nucleus affects its center, it acquires a reniform pattern; however, if it is peripheral, the nucleus has a coffee-bean shape.

It consists of a large, ovoid, mononuclear cell that is 15-25 µm in diameter, with a folded nucleus, a discrete nucleolus, and a moderate amount of slightly eosinophilic homogeneous cytoplasm. When the indentation of the nucleus affects its center, it acquires a reniform pattern; however, if it is peripheral, the nucleus has a coffee-bean shape.

Special studies are useful for definitive identification of normal and pathologic Langerhans cells. The Birbeck granule is their distinctive ultrastructural hallmark. It consists of an intracytoplasmic membranous body that is 33 nm wide and 190-360 nm long, possessing a short, rodlike shape with a dotted line down the midline of the space between the membranes (resembling a zipper) and a terminal expansion in the form of a vesicle, giving a racquet appearance. Although these granules are resistant to destruction by formalin fixation and paraffin embedding, the sensitivity of detection in such specimens is slightly decreased. Birbeck granules are rarely detected in lesions of the liver, the gastrointestinal tract, and the spleen. Langerhans cells also contain laminated substructures of lysosomes, tuboreticular structures, and trilaminar membranous loops. Note the image below.

Electron microscopy. Tennis racquet form of Birbec Electron microscopy. Tennis racquet form of Birbeck granules with a small terminal expansion.

Ultrastructural methods and enzyme histochemical studies (alpha-D-mannosidase and adenosine triphosphatase [ATPase]) have largely been replaced by immunohistochemical techniques. S-100 protein is strongly expressed in a cytoplasmic pattern, while peanut agglutinin (PNA) has a characteristic cell surface and paranuclear dot expression. LCH cells are positive for major histocompatibility (MHC) class II and CD1a. Expression of langerin (CD207), a Langerhans cell–restricted protein that induces the formation of Birbeck granules and is constitutively associated with them, is a highly specific marker of Langerhans cells. [61] The pathologic Langerhans cell expresses phenotypic markers of an activated normal Langerhans cell in its early stages. Fine-needle aspiration combined with immunohistochemistry of the cell preparation plays an important role in documenting organ involvement by LCH.

Note the images below.

High-power views. Marked epidermotropism is noted High-power views. Marked epidermotropism is noted (left). The lesional cells are large, with abundant pink cytoplasm and reniform nuclei. An admixture of inflammatory cells, including occasional eosinophils, is present (right).
High-power views. Diffuse immunoreactivity for S-1 High-power views. Diffuse immunoreactivity for S-100 protein (right). Langerhans cells and lymphocytes (left, hematoxylin and eosin).
Widespread positivity for CD1a. Note the presence Widespread positivity for CD1a. Note the presence of epidermotropism (right). Langerhans cells and lymphocytes are present in the epidermis and the papillary dermis (left, hematoxylin and eosin).

The Writing Group of the Histiocyte Society (1987) has proposed 3 levels of certainty in the diagnosis of LCH, based on clinical features, histopathology, and immunohistochemical techniques. A presumptive diagnosis is based on a typical clinical presentation and light microscopic findings. A designated diagnosis includes light microscopy in combination with positive S-100 and PNA staining studies. To make a definitive diagnosis, identification of Birbeck granules and CD1a antigens is required.


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