Langerhans Cell Histiocytosis Essay

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Langerhans Cell Histiocytosis Essay

Langerhans cell histiocytosis (LCH or histiocytosis X) is the most common form of dendritic cell type of histiocytic disorders. LCH can be divided into three groups on the basis of the number of lesions and systems involved: the unifocal (localized) form, presents between 5 and 15 years of age, in approximately 70% of LCH cases, limited to a single bone or a few bones, and may involve the lung. Multiple bones as well as the reticuloendothelial system (i.e., the liver, spleen, lymph nodes, and skin) involvement and diabetes insipidus are seen in multifocal unisystem (chronic recurring) form which constitutes approximately 20% of cases. Typically seen between 1 to 5 years of age. Langerhans Cell Histiocytosis Essay. The fatal form is the multifocal multisystem (fulminant) form comprising approximately 10% of LCH cases. Seen in the first 2 years of life and it disseminately involves the reticuloendothelial system, anemia, and thrombocytopenia. Eosinophilic granuloma, Hand-Schüller-Christian disease, and Letterer-Siwe disease are older names used when these were thought to be different diseases; these names should now be discouraged.

Langerhans cell histiocytosis is characterised by uncontrolled monoclonal proliferation of abnormal Langerhans cells, which can infiltrate ubiquitously all the tissues or organs as well as lymph nodes. The histiocytic infiltration is followed by chronic inflammation and the formation of granulomas. Uncontrolled immune response activation is the most likely etiology by an as yet unknown antigen.

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Bone lesions are seen in approximately 80% of LCH patients. LCH has a predilection to involve the flat bones with skull being the most common flat bone involved, followed by the mandible, ribs, pelvis, and spine. Skull lesions can be either asymptomatic or manifest with focal pain and soft-tissue swelling in the scalp. “Punched-out” lytic lesions are seen in skull lesions seen on radiographs with asymmetric destruction of the inner and outer cortices, which results in a characteristic bevelled edge. Mastoid bone is the classical location when temporal bone is affected. Calvarial disease lacks periosteal reaction unlike other bone lesions. The term geographic skull is used when skull lesions grow in size and coalesce, creating a map like appearance. Vertebra plana (symmetric flattening of vertebral body) is seen with involvement of spine. Diaphyseal or metaphyseal involvement seen in long bones. “Floating teeth” is seen if there is enough alveolar destruction.

Other findings include hepatomegaly with solid or cystic lesions in liver. Lymphadenopathy with cervical predominance. MRI brain will reveal absence of posterior pituitary bright spot, and thickening of pituitary stalk if there is CNS involvement. Lung involvement shows centrilobular nodules or cysts of varying sizes, with mid- to upper-lung distribution and sparing of costophrenic angles.

Meyer et al conducted a study in 1995 in Philadelphia on 42 patients. 83% of the patients had at least one affected bone. All children with lesions of the skull base (Fig 1 ) and seven of eight with facial lesions (Fig 2) had bone destruction with associated soft-tissue masses. Calvaria 13 Intracranial soft tissue 4 Skull base/face 15. Langerhans Cell Histiocytosis Essay

According to D’Ambrosio et al 2008, who did study on 100 patients in New York Ninety-six percent of the patients in this series had bone involvement. Fifty-eight of 96 patients (60%) had a solitary bone abnormality, and 38 patients (40%) had multiple lesions. By far, the most common bone involved in the series was the skull, affecting 52 of 96 patients (54%). In particular, the calvarium was affected in 45% of patients. Of the patients with calvarial involvement, the parietal bone was most commonly affected. The maxilla and/or maxillary sinus was affected in 8% of patients in the series.

In the study done by Khatami et al 2010 in Iran on 48 patients, 38 of them (79.2%) had bone involvements; skull was involved the most (66.7%), followed by Pelvis (31.3%), Femur (31.3%), Sphenoid (30.0%) and ribs (16.7%), temporal bone in 4.2%

Radiation Issue of CT

Concerns about carcinogenicity of computed tomography radiation began in the early 2000s. In recent times many examination protocols and software and hardware modifications have been made to reduce CT radiation dose. The definite risk of radiation exposure is not quantified. So, it is better to follow the principle of “As Low As Reasonably Achievable” (ALARA). This can be achieved by ensuring that the examination is clinically indicated and by keeping the radiation dose to the minimum with the help of technical advances as described below¹²⁶.

Tube current modulation is a very useful tool to control patient exposure with CT examinations. In this technique the scanner will produce less number of x-ray photons in regions of lower attenuation and higher values of tube current in regions of increased attenuation. This is of two types: Angular modulation and z-axis modulation. In angular modulation differences in attenuation in x-y plane is measured with the help of two localisers (lateral and anteroposterior views) and the tube current is modulated accordingly during rotation. In z-axis modulation the attenuation differences along the length of the patient are calculated with a single anteroposterior localiser and the tube current is modulated. The z-axis organ based tube current modulation is as much or more effective than thyroid and eye shields at reducing radiation, without the regional image noise caused by shields.

Newer reconstruction technique called iterative reconstruction significantly reduces the patient dose. In this the initial projected image is iteratively compared with the model image of the vendor. Then the algorithm intelligently decreases the noise in the image. There by a noise less image can be obtained even with a low dose CT. But this technique is more time consuming than the conventional filtered back projection technique. With the newer development of hybrid iterative reconstruction which uses both the above techniques, the speed has been considerably increased.

Accurate patient centering can also decrease the patient radiation. Other techniques such as optimization of tube potential, beam-shaping filters also make a significant contribution to dose reduction. Newer developments which hold promise to reduce the radiation dose in the future are compressed sensing, volume of interest and interior tomography techniques, and photon-counting detectors^127-136.

Low dose MDCT of PNS can be done by reducing the mAs. This is the most effective way of reducing patient exposure. The effective dose delivered by a standard dose MDCT protocol is 0.70 mSv in men and 0.76 mSv in women, whereas the effective dose delivered by a low dose MDCT protocol is 0.047 mSv in men and 0.051 mSv in women which is equivalent to standard four view radiography of PNS. Low dose CT can be used for the follow up of patients with chronic sinusitis and in tumors where the presence of soft tissue mass or bone destruction is used for follow up¹⁸.

angerhans cell histiocytosis (LCH) is an idiopathic condition characterized by proliferation of abnormal Langerhans cells (antigen-presenting immune cells). The disease has characteristics of both an abnormal reactive process and a neoplastic process. It may present initially as a rash. It can be disseminated and involve bone marrow, lungs, liver, spleen, lymph nodes, gastrointestinal (GI) tract, and the pituitary gland. Prognosis varies depending on presentation and organ involvement. LCH can occur at any age but is most common from birth to age 15 years. There is wide variation in presentation, treatment, and prognosis among individuals. Referral and long-term follow up with an oncologist are important in the management of LCH. [1][2][3]

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Etiology

The cause of LCH is unknown and continues to be a debate; however, most agree that LCH is either a reactive or neoplastic process. [4][5][6]

LGH has multiple cytokines involved, there is good survival in isolated lesions, and it can have spontaneous remissions. These characteristics support a reactive process.

However, LGH also can have organ infiltration. The widespread disease is associated with increased mortality, it typically responds to chemotherapy, and there has been at least one study that demonstrated an association with the BRAF gene mutation. These characteristics support a neoplastic process. Langerhans Cell Histiocytosis Essay.

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Epidemiology

Langerhans cell histiocytosis is rare. It occurs in 1 to 2 newborns per million per year. The incidence in children < 15 years is 4 to 5 cases per million per year. In adults, the Langerhans is about 1 to 2 cases per million per year. It may occur at any age but is more likely to occur in those < 15 years of age. [7]

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Pathophysiology

The pathophysiology of LCH is unknown. Langerhans cells are dendritic antigen-presenting cells. The abnormal cells in LCH have abnormal proliferation and lower antigen-presenting capability. LCH lesion also contains inflammatory cells and cytokines such as T lymphocytes, eosinophils, neutrophils, and macrophages. It is thought that the combination or interaction of these cells accounts for the continued proliferation of the abnormal Langerhans cells. Regardless, abnormal proliferation into tissue causes disease, based on location at presentation. For example, bone marrow infiltration may lead to decreased blood cell production.

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Histopathology

The histological features of LCH are variable and influenced by the age of lesions and their location.

The primary lesion is granulomatous with an influx of eosinophils, macrophages, T cells and multinucleated cells. The Birbeck granule is the microscopic hallmark of the disorder but may not be seen in lesions of the spleen, liver, and GI tract. Langerhans Cell Histiocytosis Essay.

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History and Physical

Symptoms and physical exam will depend on organ involvement at the time of presentation.

The rash is the most common presentation. In children, the rash may be misdiagnosed as seborrhea or atopic dermatitis but will not respond to typical treatment for these disorders. The rash of LCH ranges from a single lesion to widespread involvement. Characteristics include scaly papules, nodules, or plaques and can resemble seborrheic dermatitis. One may distinguish LCH by the presence of petechiae, bloody crusting, or firmly indurated nodules.

Bony involvement occurs in about 78% of patients. Solitary osseous lesions are usually incidentally found and may include the skull, hip/pelvis, femur, or ribs. This bony involvement may present incidentally, when obtaining imaging for another complaint, or may produce bone pain.

Pulmonary lesions occur in 20% of patients, and lymph node involvement in 30%. As such, the patient may present with pulmonary symptoms or lymphadenopathy. Hepatosplenomegaly may be present as well.

Langerhans cell histiocytosis also has a predilection for infiltration of the pituitary and causing diabetes insipidus. If this is the initial presentation, the patient may have polyuria, polydipsia, dilute urine, and hypernatremia.

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Evaluation

Biopsy of the involved site (usually skin) is required to confirm the diagnosis. Lesions will stain positive for S-100 and CD-1a. Cytoplasmic Birbeck granules will be present on electron microscopy. When the diagnosis is confirmed, workup for systemic involvement should include a skeletal survey, abdominal ultrasound, complete blood count (with bone marrow biopsy if indication of bone marrow involvement), and evaluation for diabetes insipidus. [8][9][10][9]

CT scanning or MRI

Both CT scan and MRI are invaluable for assessing the hypothalamic-pituitary area. Langerhans Cell Histiocytosis Essay. Fluorodeoxyglucose (FDG) PET scanning also is being used to assess patients with LCH. The technique is far more sensitive than bone scan for early detection of disease in the spleen, lymph nodes, and lung. In fact, FDG PET scan is now also being routinely used to monitor disease during treatment.

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Other Tests

Pulmonary function testing may help identify asymptomatic patients with lung involvement
Small bowel series is recommended in patients with failure to thrive, diarrhea, and malabsorption
Neurological and visual testing
Auditory testing
Recent studies suggest that CSF fluid can be used to detect biomarkers like glial fibrillary acidic protein to evaluate the onset of disease and response to therapy.
Skin biopsy can establish the diagnosis[11][12]

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Treatment / Management

Treatment varies greatly depending on the involved organs. If the disease is isolated, observation alone may be appropriate. Surgical removal of an isolated area is also a treatment option. Isolated skin lesions may resolve on their own, especially if they present in infancy (congenital self-healing reticulohistiocytosis), or may be treated with topical steroids, oral methotrexate, or thalidomide. Chemotherapy and radiation may be used for more systemic involved cases. There are several different chemotherapy protocols that have been used; currently, protocols are using prednisone and vinblastine, though other regimen options include vincristine, cytosine arabinoside, prednisone, cladribine, or pamidronate. [13]

Late complications are common; therefore, follow up with oncology is crucial. Complications include diabetes insipidus, growth failure, delayed puberty, tooth loss, mandibular bone loss, hearing loss, secondary cancers, neurologic/cerebellar effects, liver disease, and pulmonary fibrosis. Langerhans Cell Histiocytosis Essay.

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Prognosis

More than 50% of children under the age of 2 with disseminated Langerhans cell histiocytosis will die of the disease, but those with localized disease may have a prolonged life-span. For those who have been treated and do not have more lesions at 12 to 24 months, a full recovery can be expected. When there is lung involvement, the prognosis is not good. However, patients with isolated skin involvement and a solitary lymph node involvement tend to have a good prognosis. Langerhans Cell Histiocytosis Essay.