Histiocytosis

Question 1

Which cells are abnormally activated in histiocytic disorders?

Answer 1

The histiocytoses are a heterogenous group of disorders characterized by abnormal proliferation, activation, and cytokine release by cells involved in phagocytosis and antigen presentation, such as dendritic cells, monocytes, macrophages, and histiocytes.

Question 2

What is the median age for LCH to occur?

Answer 2

2.5 years of age

Question 3

Which is the most common of the histiocytoses?

Answer 3

Langerhans cell histiocytosis

Question 4

What are the most common early signs of LCH?

Answer 4

Gingival hypertrophy and oral ulcers.

Question 5

What are the most frequent presenting signs in LCH?

Answer 5

Skin rash in the diaper area or scalp, or lytic bone lesions, most commonly in the skull, that are often painful.

Question 6

What are some common secondary symtpoms found in patients with LCH?

Answer 6

Fever, weight loss, diarrhea, diabetes insipidus (from pituitary involvement), and a history of draining otitis.

Question 7

Which endocrine disease can be seen with LCH involving the pituitary gland?

Answer 7

Diabetes insipidus

Question 8

Which organ systems are high-risk in LCH?

Answer 8

Liver, spleen, lungs, and bone marrow.

Question 9

Which organ systems are low-risk in LCH?

Answer 9

Skin, bones, lymph nodes, and the pituitary gland.

Question 10

What are the characteristic findings on skin biopsy in patients with LCH?

Answer 10

A large number of pathologic Langerhans cells, along with lymphocytes, macrophages, granulocytes, eosinophils, and multinucleated giant cells.

Question 11

What immunohistochemistry findings are diagnostic for Langerhans Cell Histiocytosis?

Answer 11

CD1a or CD207 (langerin)

Question 12

What is the characteristing finding on electron microscopy for patients with LCH?

Answer 12

Birbeck granules. *** Picture?

Question 13

What is the prognosis in low-risk vs high-risk patients diagnosed with Langerhans Cell Histiocytosis?

Answer 13

Low-risk patients have cure rates >90%. High-risk patients can have mortality approaching 50%.

Question 14

Distinguish between primary and secondary HLH.

Answer 14

Primary HLH is a rare autosomal recessive disorder that usually occurs before one year of age. Secondary HLH occurs later, with EBV and other infections acting as a trigger.

Question 15

In what clinical scenario should HLH be suspected?

Answer 15

Suspect HLH in children with cytopenias and hepatosplenomegaly.

Question 16

What laboratory findings would you expect in a patient with HLH?

Answer 16

Pancytopenia, hyperferritinemia, hypertriglyceridemia, and hypofibrogenemia.

Question 17

What are the diagnostic criteria for HLH?

Answer 17

Diagnosis requires that at least five of the following criteria be met: Fever, splenomegaly, peripheral blood cytopenia of ≥2 lineages, hypertriglyceridemia and/or hypofibrinogenemia, hemophagocytosis without evidence of malignancy in bone marrow, spleen, or lymph nodes, elevated serum ferritin, low or absent natural killer (NK) cell activity, elevated soluble IL-2 receptor (soluble CD25)

Question 18

What is first line therapy for patients with HLH?

Answer 18

Dexamethasone and etoposide. If CNS disease is present, methotrexate is given as well.

Question 19

When is bone marrow transplant indicated in patients with HLH?

Answer 19

Bone marrow transplant is indicated in patients with primary HLH or children with secondary HLH who are refractory to chemotherapy, or who relapse.