SOLID TUMORS

HODGKIN LYMPHOMA

• It can affect children at any age, but is more common in children over five years old. Hodgkin lymphoma can also occur in young adults. During childhood, boys are more often affected, but in the teenage years boys and girls are affected equally.

• Hodgkin lymphoma was first described by Dr Thomas Hodgkin in 1832. It is a cancer that affects the lymphatic system.

• Hodgkin's lymphoma is rare in children under 5 years of age. In children under age 10, it is more common in boys than girls. About 10% to 15% of all cases of Hodgkin's are diagnosed in children 16 and under

• What differentiates Hodgkin's lymphoma is the presence of Reed-Sternberg cells (and variations on this cell) in the cancerous area, a cell specific to Hodgkin's Disease. There is definitive evidence that the the cancerous cells are B-cell lymphocytes (white blood cells). The Epstein-Barr virus (EBV) also appears to be a factor, at least in some cases - appearing in about 40-50% of Hodgkin's cases.   It has recently been found that Interleukin-13, a natural cytokine in the body, may be overproduced by Hodgkin's cancerous cells.  What causes Hodgkin's lymphoma is still being researched.

• Types of Hodgkin's Lymphoma: • Nodular sclerosis (NS). The lymph nodes in the lower neck,

chest and collarbone usually contain normal and reactive lymphocytes and Reed-Sternberg cells separated by bands of scar-like tissues.

• Lymphocyte predominance (LP). The lymph nodes are composed largely of reactive lymphocytes and malignant L&H cells which have a "popcorn" appearance and very few Reed-Sternberg cells.

• Mixed cell (MC). The lymph nodes usually contain Reed-Sternberg cells and inflammatory cells.

• Lymphocyte depleted (LD). There are two different variations of this classification: one with sheets of differing malignant cells; the other with few Reed-Sternberg cells and lymphocytes with scar-like tissue.

• Nodular lymphocyte predominance Hodgkin's lymphoma

SIGNS AND SYMPTOMS• The first sign of Hodgkin lymphoma is usually a painless

swelling of one gland, or a group of lymph glands, which continues for some weeks. The first glands to be affected are usually in the neck, most often on one side only, in a small area above the collarbone.

• Sometimes, enlarged glands can be felt in the armpit or groin.

• If glands in the chest are affected, this can cause a troublesome cough or breathlessness.

• Occasionally, a child with Hodgkin lymphoma may have a high temperature (fever), night sweats, severe itching or weight loss.

POSITIVE DIAGNOSIS

• biopsy

• x-rays, CT and MRI scans and blood tests, are carried out to find the exact size and position of the lymphoma and whether it has spread. If a blood test suggests that the bone marrow is affected by the cancer, a bone marrow sample may be taken.

STAGING• Stage 1 One group of lymph nodes is affected but the

lymphoma is only on one side of the diaphragm• Stage 2 Two or more groups of lymph nodes are affected

and the lymphoma is only on one side of the diaphragm. • Stage 3 There are lymphoma cells in the lymph nodes

above and below the diaphragm. The spleen may also be affected.

• Stage 4 The lymphoma has spread beyond the lymph nodes, for example to the liver, lungs or bone marrow

• As well as giving each stage a number, there is a letter code – either A or B – to show if the child has the following specific symptoms: fever, significant weight loss (more than a tenth of their body weight in the last six months) or night sweats ;none of these the lymphoma will be classified as A, and if they do have these symptoms it is classified as B.

• A physical exam including examining the lymph nodes • Collecting a medical history and history of symptoms • A complete blood work-up including checks for abnormal 

blood cell count, blood chemistry, and abnormal sedimentation rate • A chest x-ray to view lymph nodes and to see if other organs are involved • A computerized tomography (CT or CAT) scan,

positron emission tomography (PET) scan and/or magnetic resonance imaging (MRI) scan of the chest, pelvis, and abdomen to determine the possible spread of the disease

• A gallium scan to check for radioactive intake of gallium in the lymph system indicating swelling and ultimately disease

• A bone marrow aspiration and biopsy to determine if the bone marrow has been affected by lymphoma; in this procedure the hip is numbed (ask for EMLA cream or similar to numb the site beforehand at home) and a needle is inserted into the bone; liquid bone marrow and a bone chip are extracted and the tissue is examined under a microscope

• Certain medical centers may perform additional tests, including • Exploratory surgery (staging laparotomy) to determine the extent of the

disease. In some cases the spleen is removed if it is the only organ affected.  A tissue sample may also be taken of the liver. The child may receive medicine to prevent infection.

• A lymphangiogram, a procedure during which a radio-opaque liquid is injected into the lymph system through the feet; the fluid travels throughout the lymph system and remains visible by x-rays for up to six months

• Hodgkin lymphoma in children is treated with chemotherapy, but sometimes radiotherapy is also needed. For very localised disease (when the cancer has not spread beyond its original site) radiotherapy alone may be used. The type and amount of treatment depends on the stage of the disease at diagnosis.

• Side effects can include nausea and vomiting, hair loss, an increased risk of infection or bruising and bleeding, tiredness and diarrhoea.

Chemotherapy• The mainstream chemotherapy regimens is: • ABVD - Adriamycin (Doxorubicin), Bleomycin, Vinblastine

(Velban), Dacarbazine (DTIC) • Other regimens that have been or might be used are:• MOPP - Mechlorethamine, Vincristine, Prednisone,

Procarbazine • MOPP alternating with ABV • MOPP alternating with ABVD • ChlVPP - Chlorambucil, Vinblastine, Procarbazine,

Prednisone • Chemotherapy is given in measured doses.  Often a

chemotherapy regimen will be given in cycles - treatments spaced over the period of days.  For example, it is common to give ABVD in 4 week cycles.  Two treatments, one every 2 weeks would be in one cycle. The number of cycles vary but for example 6 cycles would consist of 12 treatments spaced two weeks apart.

• Adriamycin 25 mg/m2 IV on days 1 and 15

• Bleomycin 10 units/m2 IV on days 1 and 15

• Vinblastine 6 mg/m2 IV on days 1 and 15

• Dacarbazine375 mg/m2 IV on days 1 and 15

NON HODGKON’S LYMPHOMA

• Non-Hodgkin's lymphoma is cancer in the lymphatic system. According to estimates by the Leukemia and Lymphoma Society, almost 85 percent of lymphomas diagnosed in the US in 2006 were non-Hodgkin's lymphoma.

• Lymphomas are the fifth most common childhood cancer. They occur most often in children between the ages of 7 and 11, but can occur at any age from infancy to adulthood.

• Non-Hodgkin's lymphoma affects males more often than females, and is more common among Caucasian children than among African-American children and children of other races.

• Lymphoblastic non-Hodgkin's lymphoma accounts for about 30 percent of the cases, involves the T-cells, and usually presents with a mass in the chest, swollen lymph node(s), with or without bone marrow and central nervous system involvement.

• Burkitt's or non-Burkitt's lymphomaBurkitt's or non-Burkitt's lymphoma is a non-Hodgkin's disease in which the cells are undifferentiated and diffuse. This has also been referred to as small non-cleaved cells. Burkitt's and non-Burkitt's lymphoma accounts for about 40 to 50 percent of the cases and is usually characterized by a large abdominal tumor and may have bone marrow and central nervous system involvement.

• large cell or diffuse histiocytic non-Hodgkin's lymphomaLarge cell or diffuse histiocytic non-Hodgkin's involves the B-cells and T-cells and accounts for about 25 percent of the cases. Children with this type of non-Hodgkin's lymphoma usually have lymphatic system involvement, as well as a non-lymph structure (i.e., lung, jaw, brain, skin, and bone) involvement.

CLASIFICATION REAL

Diffuse Large B-cell Lymphoma Cells are large, with prominent nucleoli and abundant cytoplasm and many mitoses. Most are B-cell, but 20% are T-cell phenotype

CD19, 20, 79a; some have t(14;18); some have Bcl-2 and Bcl-6 expression; linked to EBV infection; negative TdT

Though often localized, they tend to be aggressive extranodal masses; seen in adults and children, also in HIV infection

Burkitt Lymphoma Intermediate sized B-lymphocytes (small-noncleaved cells)

CD10, 19, 20, 79a; t(8:14) is characteristic; African form linked to EBV infection; negative TdT

Endemic in Africa with mandibular and abdominal involvement; sporadic elsewhere with abdominal involvement; affects mainly children and young adults

High-grade B-cell Lymphoma (small non-cleaved) Burkitt-like Lymphoma

Intermediate sized B-lymphocytes (small non-cleaved cells)

CD19, 20 Sporadic; may be seen with HIV infection

Precursor T or B-cell Lymphoblastic Lymphoma/Leukemia (Lymphoblastic Lymphoma

Intermediate sized lymphocytes in a diffuse pattern

B-cells are CD19, 20, sometimes CD10; T-cells are CD3 and 8; all are TdT positive

Seen in children and adolescents; T-cell type often in mediastinum; very aggressive and can progress to acute lymphocytic leukemia

B CELL LARGE LYMPHOMA

CLINICS

• painless swelling of the lymph nodes in neck, chest, abdomen, underarm, or groin

• fever • sore throat • fullness in groin area from node involvement • bone and joint pain • night sweats • tiring easily (fatigue) • weight loss/decreased appetite • itching of the skin • recurring infections

STAGING

• stage I - involves the tumor at one site, either nodal or elsewhere in the body.

• stage II - involves the tumor at two or more sites on the same side of the body.

• stage III - involves tumors in any number that occur on both sides of the body, but does not involve bone marrow or the central nervous system.

• stage IV - any stage of tumor that also has bone marrow and/or central nervous system involvement. Stage IV is also subdivided depending on the amount of blasts (cancer cells) present in the bone marrow.

TESTS• Blood ( CBC, ESR, Fg,ALT, BUN) , urine tests • x-rays of the chest• computed tomography scan of the abdomen, chest, and pelvis positron

emission tomography (PET) scan - radioactive-tagged glucose (sugar) is injected into the bloodstream. Tissues that use the glucose more than normal tissues (such as tumors) can be detected by a scanning machine. PET scans can be used to find small tumors or to check if treatment for a known tumor is working.

• lymph node biopsy• lymphangiogram • bone marrow aspiration and/or biopsy examins the number, size, and

maturity of blood cells and/or abnormal cells. • lumbar puncture (to evaluate central nervous system disease for cancer

cells ) - a special needle is placed into the lower back, into the spinal canal. This is the area around the spinal cord. A small amount of cerebral spinal fluid (CSF) can be removed and sent for testing. CSF is the fluid which bathes the brain and spinal cord.

TREATMENT

• chemotherapy • radiation therapy • surgery • close monitoring of blood work • bone marrow transplant • bone marrow examinations • lumbar punctures/spinal taps • antibiotics (to prevent or treat infections ) • supportive care (for side effects of treatment ) • long-term follow up care (to determine response to treatment,

detect recurrent disease, and manage late effects of treatment)

WILMS' TUMOR

• Over the past few decades, dramatic improvement has occurred in the survival of children with Wilms' tumor. This excellent outcome is attributed primarily to the availability of several active chemotherapeutic agents; however, advances in radiation oncology, supportive care, and improved surgical and anesthetic techniques also have a role.

• The total annual incidence of Wilms' tumor in the United States is estimated at 450 to 500 cases.

• The median age of presentation is 36.5 months for boys compared with 42.5 months for girls with unilateral tumors.

• Wilms' tumor presents almost equally in males and females; however, there is a higher incidence in African or African-American children when compared with Caucasian or Asian children.

• Several associated congenital anomalies, including aniridia, hemihypertrophy, cryptorchidism, and hypospadias, have been reported.

• Genitourinary anomalies (hypospadias, cryptorchidism, other genital anomalies, renal fusion anomalies) are present in 4.5% of patients with Wilms' tumor.

• The specific association of male pseudohermaphroditism, renal mesangial sclerosis, and nephroblastoma is known as Denys-Drash syndrome.

• Hemihypertrophy may occur alone or as part of the Beckwith-Wiedemann syndrome,

• The incidence of aniridia in patients with Wilms' tumor is 1.1%.

• Aniridia and Wilms' tumor are most commonly associated in patients with the WAGR syndrome ( Wilms tumor, aniridia, genital anomalies, and mental retardation).

• Most affected individuals have a constitutional deletion on chromosome 11, and the incidence of Wilms' tumor is 42%.

• Histology is one of the most important determinants of outcome in children with Wilms' tumor.

• Wilms' tumor simulates the development of a normal kidney with blastemal, epithelial (tubules), and stromal components

• Favorable histology is defined as the lack of findings of anaplasia

• Blastemal-predominant tumors behave more aggressively and present with early metastasis and advanced disease.

CLINICAL EVALUATION AND STAGING

• Most patients are diagnosed by their primary care physician after an abdominal enlargement or mass is noted in routine care of the child.

• The child may also present with acute or chronic abdominal pain, hematuria, or fever. The child should be examined carefully, with particular attention to associated anomalies such as aniridia, hemihypertrophy, macroglossia, or genitourinary malformations.

• The patient should be examined for signs of venous obstruction, such as varicocele, prominent veins over the abdominal wall, or leg swelling.

• The abdominal examination should attempt to differentiate this mass from benign causes such as hepatomegaly or splenomegaly and from other malignancies such as neuroblastoma.

Imaging• Preoperative diagnosis through accurate imaging is an

important part of the evaluation of a child with Wilms' tumor. • Although CT is often performed, the most useful initial study

is ultrasonography. The goal of imaging should be to localize the source of the mass, identify associated genitourinary anomalies, confirm the presence of a functioning contralateral kidney, and exclude extension of tumor into the inferior vena cava. Ultrasound is useful in determining the origin of the mass and in assessing the inferior vena cava but is of limited value in assessing renal function.

• Chest radiography should be performed to ensure that there is no metastatic disease. CT of the chest may detect lesions not seen on plain film, and the management of these patients is somewhat controversial

• Stage I. The tumor is limited to the kidney and was completely excised. The renal capsule has an intact outer surface.The tumor was not ruptured or manipulated for a biopsy prior to removal (fine-needle aspiration biopsies areexcluded from this restriction). The vessels of the renal sinus are not involved.

• Stage II. The tumor extends beyond the kidney but was completely excised. There may be regional extension oftumor (i.e., penetration of the renal capsule or extensive invasion of the renal sinus).

• Stage III. Residual nonhematogenous tumor is present and confined to the abdomen. Any one of the following mayoccur: (1) Lymph nodes within the abdomen or pelvis are found to be involved by tumor (renal hilar, para-aorticor beyond). Lymph node involvement in the thorax or other extra-abdominal sites would be a criterion for stageIV. (2) The tumor has penetrated through the peritoneal surface. (3) Tumor implants are found on the peritonealsurface. (4) Gross or microscopic tumor remains postoperatively (e.g., tumor cells are found at the margin ofsurgical resection on microscopic examination). (5) The tumor is not completely resectable because of localinfiltration into vital structures. (6) Tumor spill not confined to the flank occurred either before or during surgery.

• Stage IV. Hematogenous metastases (e.g., lung, liver, bone, brain), or lymph node metastases outside theabdominopelvic region are present.

• Stage V. Bilateral renal involvement is present at diagnosis. An attempt should be made to stage each side accordingto the above criteria on the basis of the extent of disease prior to biopsy or treatment.

TREATMENT

• patients with stage I favorable histology Wilms' tumor were treated successfully with either a 10-week or 18-week regimen of vincristine and actinomycin D

• Preoperative treatment can produce a dramatic reduction in the size of the primary tumor, facilitating surgical excision; however, the staging information obtained following prenephrectomy chemotherapy does not reflect the original tumor stage

• The surgeon has an important role in the management of Wilms' tumor. Careful removal of the tumor without rupture or spill is mandatory because these patients have a sixfold increase in local abdominal relapse

NEUROBLASTOMA• Neuroblastoma is the most common extracranial

solid tumor in infancy. It is an embryonal malignancy of the sympathetic nervous system arising from neuroblasts (pluripotent sympathetic cells). In the developing embryo, these cells invaginate, migrate along the neuraxis, and populate the sympathetic ganglia, adrenal medulla, and other sites. The pattern of distribution of these cells correlates with the sites of primary disease presentation.

• In the U.S., approximately 650 children are diagnosed with neuroblastoma each year. It is often present at birth, but not detected until the tumor begins to grow and compress the surrounding organs. Most children affected by neuroblastoma have been diagnosed before the age of 5.

• Origin and migration pattern of neuroblasts during fetal development explains the multiple anatomic sites where these tumors occur; location of tumors appears to vary with age. Tumors can occur in the abdominal cavity (40% adrenal, 25% paraspinal ganglia) or can involve other sites (15% thoracic, 5% pelvic, 3% cervical tumors, 12% miscellaneous). Infants more commonly present with thoracic and cervical tumors, whereas older children more frequently have abdominal tumors.

• Stage of the tumor at the time of diagnosis and age of the patient are the most important prognostic factors. Although patients with localized tumors (regardless of age) have an excellent outcome (80-90% 3-year event-free survival [EFS] rate), patients older than 1 year with metastatic disease fare poorly. Generally, more than 50% of patients present with metastatic disease at the time of diagnosis, 20-25% have localized disease, 15% have regional extension, and approximately 7% present during infancy with disseminated disease limited to the skin, liver, and bone marrow (stage 4S).

HISTOLOGY

• The undifferentiated neuroblastomas histologically present as small, round, blue cell tumors with dense nests of cells in a fibrovascular matrix and Homer-Wright pseudorosettes. These pseudorosettes, which are observed in 15-50% of tumor samples, can be described as neuroblasts surrounding eosinophilic neuritic processes. The typical tumor shows small uniform cells with scant cytoplasm and hyperchromatic nuclei. A neuritic process, also called neuropil, is a pathognomonic feature of neuroblastoma cells. NSE, chromogranin, synaptophysin, and S-100 immunohistochemical stains are usually positive

CLINICS• Tumors that arise from the paraspinal sympathetic ganglia can grow

through the spinal foramina into the spinal canal and impinge on the spinal cord. This may result in the presence of neurologic symptoms, including weakness, limping, paralysis, and even bladder and bowel dysfunction.

• Thoracic neuroblastomas (posterior mediastinum) may be asymptomatic and are usually diagnosed by imaging studies obtained for other reasons. Presenting signs or symptoms may be insignificant and involve mild airway obstruction or chronic cough, leading to chest radiography.

• Because more than 50% of patients present with advanced-stage disease, usually to the bone and bone marrow, the most common presentation includes bone pain and a limp. However, patients may also present with unexplained fever, weight loss, irritability, and periorbital ecchymosis secondary to metastatic disease to the orbits. The presence of bone metastases can lead to pathologic fractures.

• Approximately two thirds of patients with neuroblastoma have abdominal primaries. In these circumstances, patients can present with an asymptomatic abdominal mass that usually is discovered by the parents or a caregiver.

TESTS• More than 90% of patients have elevated homovanillic acid (HVA) and/or

vanillylmandelic acid (VMA) detectable in urine. • Serum LDH (useful as biologic marker) • Ferritin (useful as biologic marker) • CBC count and differential (Anemia or other cytopenias suggest bone

marrow involvement.) • CBC, ESR,BUN.ALT, Total bilirubin • Alkaline phosphatase • Total protein • Albumin • Prothrombin time (PT)/activated prothrombin time (aPTT)• Electrolytes • Calcium • Magnesium • Uric acid

• Obtain chest and abdominal radiographs to evaluate for the presence of a posterior mediastinal mass or calcifications.

• A CT scan of the primary site is essential to determine tumor extent. The main body of the tumor is usually indistinguishable from nodal masses.

• In cases of paraspinal masses, MRI aids in determining the presence of intraspinal tumor and cord compression.

• I123/131-methyliodobenzylguanadine (MIBG) accumulates in catecholaminergic cells and provides a specific way of identifying primary and metastatic disease if present. Increasing numbers of institutions have access to MIBG scanning.

• A technetium-99 bone scan can also be used to evaluate bone metastases. Especially in patients with negative MIBG study findings.

• Skeletal surveys may also be useful, especially in patients with multiple metastatic lesions.

• Positron emission tomography (PET) scan are under evaluation.

TREATMENT

• SURGERY

• CHEMOTHERAPY

• RADIOTHERAPY

Classification of Histiocytosis

EM demonstrating ultrastructural Birbeck granules (cluster between two arrows).

Unifocal LCH (eosinophilic granuloma of bone)

• Age: 5-15 years• Solitary calvarial lesion in young

adults; other sites of involvement include the vertebra, the rib, the mandible, the femur, the ilium, and the scapula .

• Asymptomatic or painful.

Multifocal LCH (Hand-Schuller-Christian disease)

• Age: 2-10 years• Fever, diffuse eruption(scalp, ear canal),

otitis media, mastoiditis, URI, bone lesions, mild lymphadenopathy, hepatomegaly, and splenomegaly.

• Diabetes insipidus (posterior stalk of the hypothalamus)

• Hand-Schűller-Christian triad: calvarial bone defects, diabetes insipidus, exophthalmos

Acute disseminated LCH (Letter-Siwe disease)

• Age: <2 y/o• Aggressive systemic disorder

• fever; anemia; thrombocytopenia; pulmonary infiltrates; skin lesions; and enlargement of the lymph nodes, the spleen, and the liver

• Rapid fatal if untreated• With intensive chemotherapy, 5-year survival is

about 50%

Clinical Presentation

• Bone• Skin• Hypothalamic/Pituitary axis• Other endocrinopathies• CNS• Lymph nodes• Hepatic enlargement• Others

Bone

• The most common manifestation (80~100% )• Skull (27%), femur (13%), mandible/maxilla (11%),

pelvis (10%), vertebral bodies (8%), ribs (8%), humerus (5%), and tibia (3%)

• The bones of the hands and feet usually spared.

Skin

• Up to 50% with multisystem disease may initially present with a rash.

• Often the first sign of multisystem LCH

• Scaly, erythematous, seborrhea-like brown to red papules, presenting in a fashion similar to contact dermatitis

Hypothalamic/Pituitary axis

• Hypothalamic involvement:disturbances in behavior, appetite, temperature regulation, or sleep patterns.

• Posterior pituitary involvement: DI

Other endocrinopathies• Growth retardation

• Thyroid hormone deficiency

• Precocious or delayed puberty, amenorrhea, and hypocortisolism

CNS

• Cognitive impairment, emotional lability, changes in behavior, neurologic dysfunction, pyramidal signs, cerebellar symptoms, and cranial nerve palsy (causing difficulties in speech and swallowing)

• The most common manifestation is cerebellar symptoms, followed by pyramidal signs and cranial nerve palsy

Lymph node

• Lymph nodes are sometimes enlarged in LCH patients (less than 10%), with those from the head and neck region preferentially affected

Hepatic enlargement

• Very common in people with disseminated disease (up to 1/3 to 1/2 of children with disseminated disease have hepatomegaly) Signify a later stage of multisystemic disease or a manifestation of a more fulminant disease process

Lung disease

• Respiratory distress with tachypnea, retraction, and persistent cough

• lung disease is most common in adult LCH patients.

• Children with uncontrolled LCH may develop chronic respiratory failure, presenting with cysts or bullae

Treatment

• Single-agent chemotherapy is the first line therapy.(carboplatin, 2-chlorodeoxyadenosine, chlorambucil, cyclophosphamide, cytosin, arabinoside, daunomycin, etoposide, mercaptopurine, methotrexate, mechlorethamine, procarbazine, vinblastine, vincristine, vindesine)

• Topical steroid, intralesional injection of steroids, NSAID, phototherapy, bone marrow allografting, hematopoietic stem cell transplantation, cyclosporin A,prednisoe.

Unifocal LCH (eosinophilic granuloma of bone)

• Age: 5-15 years• Solitary calvarial lesion in young

adults; other sites of involvement include the vertebra, the rib, the mandible, the femur, the ilium, and the scapula .

• Asymptomatic or painful.

Multifocal LCH (Hand-Schuller-Christian disease)

• Age: 2-10 years• Fever, diffuse eruption(scalp, ear canal),

otitis media, mastoiditis, URI, bone lesions, mild lymphadenopathy, hepatomegaly, and splenomegaly.

• Diabetes insipidus (posterior stalk of the hypothalamus)

• Hand-Schűller-Christian triad: calvarial bone defects, diabetes insipidus, exophthalmos

Acute disseminated LCH (Letter-Siwe disease)

• Age: <2 y/o• Aggressive systemic disorder

• fever; anemia; thrombocytopenia; pulmonary infiltrates; skin lesions; and enlargement of the lymph nodes, the spleen, and the liver

• Rapid fatal if untreated• With intensive chemotherapy, 5-year survival is

about 50%

Clinical Presentation

• Bone• Skin• Hypothalamic/Pituitary axis• Other endocrinopathies• CNS• Lymph nodes• Hepatic enlargement• Others

Bone

• The most common manifestation (80~100% )• Skull (27%), femur (13%), mandible/maxilla (11%),

pelvis (10%), vertebral bodies (8%), ribs (8%), humerus (5%), and tibia (3%)

• The bones of the hands and feet usually spared.

Skin

• Up to 50% with multisystem disease may initially present with a rash.

• Often the first sign of multisystem LCH

• Scaly, erythematous, seborrhea-like brown to red papules, presenting in a fashion similar to contact dermatitis

Hypothalamic/Pituitary axis

• Hypothalamic involvement:disturbances in behavior, appetite, temperature regulation, or sleep patterns.

• Posterior pituitary involvement: DI

Other endocrinopathies• Growth retardation

• Thyroid hormone deficiency

• Precocious or delayed puberty, amenorrhea, and hypocortisolism

CNS

• Cognitive impairment, emotional lability, changes in behavior, neurologic dysfunction, pyramidal signs, cerebellar symptoms, and cranial nerve palsy (causing difficulties in speech and swallowing)

• The most common manifestation is cerebellar symptoms, followed by pyramidal signs and cranial nerve palsy

Lymph node

• Lymph nodes are sometimes enlarged in LCH patients (less than 10%), with those from the head and neck region preferentially affected

Hepatic enlargement

• Very common in people with disseminated disease (up to 1/3 to 1/2 of children with disseminated disease have hepatomegaly) Signify a later stage of multisystemic disease or a manifestation of a more fulminant disease process

Lung disease

• Respiratory distress with tachypnea, retraction, and persistent cough

• lung disease is most common in adult LCH patients.

• Children with uncontrolled LCH may develop chronic respiratory failure, presenting with cysts or bullae

Treatment

• Single-agent chemotherapy is the first line therapy.(carboplatin, 2-chlorodeoxyadenosine, chlorambucil, cyclophosphamide, cytosin, arabinoside, daunomycin, etoposide, mercaptopurine, methotrexate, mechlorethamine, procarbazine, vinblastine, vincristine, vindesine)

• Topical steroid, intralesional injection of steroids, NSAID, phototherapy, bone marrow allografting, hematopoietic stem cell transplantation, cyclosporin A,prednisoe.