Langerhans Cell Histiocytosis in Children

What is Langerhans Cell Histiocytosis?

LCH stands for Langerhans cell histiocytosis, previously known as histiocytosis X. Characterized by the clonal proliferation of Langerhans cells and tissue infiltration by histiocytes. It shows a wide spectrum from locally invasive, sometimes spontaneous aggression to a multi-system disseminated illness that can have severe manifestations and long-term complications. The peak age is 0–15 years, and males >> females. The sites of involvement are bones—80% (skull bones are the most affected), skin (60%), lymph node (33%), liver, and spleen (20%). More than 50% of the cases are associated with the BRAF V600E mutation. It is a point mutation of BRAF, which changes valine V to glutamate E at the 600th position. It is more of a sporadic mutation than an inherited mutation.

Understand the Concepts of LCH

LCH is due to mutations or abnormalities in the MAP kinase pathway. The LCH cell is not a (differentiated) Langerhans cell but rather an immature cell of myeloid origin, possibly in an arrested state of development. So, the cell of origin is still an area of research. It is an immature myeloid cell that has not developed and tends to develop features of tumor markers suggestive of Langerhans cell.

Also read: Germ Cell Tumors In Children

Clinical Classification of LCH

Unisystem

Unifocal

Eosinophilic granuloma

↓

Isolated bony involvement

Lytic lesions in the skull

↓

Single > multiple

Well defined, sharply demarcated

Little to no reactive bone formation

Multifocal

Hand-Schuller-Christian disease

↓

Skull, facial bones

Underlying CNS inside skull is also involved

Triad of LCH

Diabetes insipidus

Exophthalmos (Accumulation of granulation tissue in orbit)

Calvarial bone/scale defects

Multi system

Letterer-Siwe Disease

Disease of unisystem disease may be seen PLUS

• Fever, weight loss
• Hepatic cirrhosis
• Sclerosing cholangitis
  • BM- Anemia, thrombocytopenia
  • CNS-Ataxia, Gliosis

Also read: Types Of Liver Transplantation In Children

Other Features

Skin: seborrheic dermatitis-like rash on the scalp and the diaper regions.

Skin involvement is seen in 50% of the cases. Azoles and salicylic acid respond to dermatitis; dermatitis (seborrheic) is refractory to therapy. It is a scaly, dandruff-like rash.

Lymphadenopathy was seen in almost 33% of the patients. Generalized, or it may be a specific group of lymph nodes that are involved. So non-tender lymphadenitis is seen. Secondary infections can produce tender lymphadenitis. Hepatosplenomegaly is seen in 20% of the cases.

Otitis media may be present with or without effusion. Pulmonary infiltrates may be present, tending to produce a pneumonia-like condition, which can be seen in CT and chest X-rays.

Pneumothorax can be seen. Almost 30% of the patients have either pulmonary

infiltrates or pneumothorax. Honeycomb lung is seen in LCH. In LCH patients, the unisystem unifocal type is usually asymptomatic; other forms may be associated with failure to thrive.

Any cases of failure to thrive with seborrheic dermatitis must be taken seriously.

Diagnosis of LCH

The investigation of choice is a biopsy of the lesion. Histopathology and immunohistochemistry (IHC) are performed. H and E stain: Infiltration with histiocytes, or Langerhans cells, eosinophils, and macrophages is seen. On IHC, Langerhans cells are positive for the following tumor markers:.

• CD1a
• CD207 or Langerin is more sensitive than CD1a
• S-100
• MHC-II or HLA-DR

Electron microscopy: Birbeck granules, tennis racket-shaped, and the handle shows a zipper-like appearance.

Also read: Leukemias In Children

Treatment

Localized disease or a single bony lesion: curettage, local RT, or intralesional steroid injection (like triamcinolone) is given. Approximately 25–50% of small, single solitary lesions show spontaneous regression. Multifocal and multisystemic disease: chemotherapy (Vinblastine + Etoposide + 6-Mercaptopurine + steroids) is done. Refractory disease: stem cell transplant and cladribine (most effective) are given.

Concept of “Risk Organs” in LCH

3 organ systems are considered risk organs:

Liver, spleen, and bone marrow

Involvement of risk organs portends a poor prognosis and is associated with an aggressive disease CNS involvement is also associated with poor prognosis, but CNS is not considered to be a risk organ. If CNS is associated with gliosis, then it's a poor prognosis that is rarely seen

Pulmonary fibrosis and hepatic cirrhosis are permanent and do not reverse with therapy.

Some patients may develop poorly understood late-onset progressive neurodegeneration related to gliosis of the CNS.

Also read: High-Yield NEET SS Pediatric Oncology Questions

Hope you found this blog helpful for your NEET SS Pediatrics Oncology preparation. For more informative and interesting posts like these, keep reading PrepLadder’s blogs.