Chapter 13: Langerhans Histiocytosis + Spleen and Thymus

Question 1

Most common mutation in Langerhans Cell Histiocytosis?

Answer 1

Valine-to-glutamate substitution at residue 600 in BRAF (same as Hairy Cell Leukemia)

Question 2

Characteristic morphological finding of the Langerhans Cells in histiocytosis?

Answer 2

Birbeck granules in cytoplasm (Tennis racket-like)

Question 3

Tumor cells of Langerhans Cell Histiocytosis typically express what 3 markers?

Answer 3

HLA-DR, S-100, and CD1a

Question 4

Multifocal multisystem Langerhans cell histiocytosis (Lettere-Siwe disease) most often occurs in whom; characterized by what?

Answer 4

• Children <2 y/o
• Seborrheic eruptions of trunk and scalp + osteolytic bone lesions
• Hepatosplenomegaly + LAD + pulmonary lesions
• Anemia, thrombocytopenia and reuccrent infections, such as otits media and mastoiditis

Question 5

Prognosis of multifocal multisystem Langerhans cell histiocytosis (Lettere-Siwe disease)?

Answer 5

Untreated = rapidly fatal; with intense chemo 50% survive 5 years

Question 6

What are the characteristic findings of unifocal unisystem Langerhans cell histiocytosis (eosinophilic granuloma)?

Answer 6

• Skeletal lesions in older children, rarely adults
• Most common in the calvarium, ribs, and femur –> pathologic fractures

Question 7

What are the characteristic findings of multifocal (Hands-Schuller-Christian disease) unisystem Langerhans cell histiocytosis

Answer 7

• Multiple erosive bony masses in young child
• 50% have diabetes insipidus
• Hand-Schuller-Christian triad: calvarial bone defects, diabetes insipidus, and exopthalmos

Question 8

What is course of unifocal and multifocal unisystem Langerhans cell histiocytosis (eosinophilic granuloma); how is each treated?

Answer 8

• Many patients experience spontaneous regression
• Chemotherapy if multifocal
• Local excision or irradiation if unifocal

Question 9

Pulmonary Langerhans histiocytosis is most often seen in whom; characteristics?

Answer 9

• Most often in adult smokers
• Multiple fine nodules and cysts in the middle and upper lung zones
• May regress after cessation of smoking

Question 10

Which benign neoplasms are the most common in the spleen?

Answer 10

• Hamartomas
• Hemangiomas
• Lymphangiomas

Question 11

Major morphological feature of nonspecific acute splenitis?

Answer 11

Acute congestion of the red pulp, may efface the lymphoid follicles

Question 12

What is seen in hypersplenism and it’s often due to what?

Answer 12

• Becomes ↑ active –> anemia, leukopenia, and thrombocytopenia
• Often seen in setting of splenomegaly, but is most common 2’ to portal HTN and hematologic disorders

Question 13

What are the 3 most common causes of congestive splenomegaly?

Answer 13

• Cirrhosis of liver = most common; alcoholics or schistosomiasis
• Portal or splenic vein thrombosis
• Cardiac failure; especially right-sided

Question 14

Characteristic morphology of the spleen in long-standing congestive splenomegaly?

Answer 14

• Organ is firm and capsule is thickened and fibrous
• Red pulp becomes fibrotic over time
• Resultant slowing of blood, prolongs exposure of blood cells to macrophages, resulting in excessive destruction (hypersplenism)

Question 15

What are common causes of occlusion of splenic arteries by emboli leading to splenic infarction?

Answer 15

• Cardiac emboli and sickle cell disease
• May occur in infectious endocarditis
• Splenomegaly, regardless of cause

Question 16

Which congenital anomaly of the spleen is common; significance?

Answer 16

• Accessory spleen(s)
• Important to recognize in diseases with splenectomy as tx, such as hereditary spherocytosis and ITP

Question 17

Most common causes of splenic rupture?

Answer 17

• Most often due to blunt trauma
• Predisposing conditions = infectious mononucleosis, malaria, typhoid fever, and lymphoid neoplasms
• Rupture leads to intraperitoneal hemorrhage

Question 18

What is clinical significance of cytic thymic lesion in symptomatic pt?

Answer 18

Should provoke thorough search for neoplasm, particularly a lymphoma or thymoma

Question 19

Why is thymic hyperplasia a misleading term, what does it actually refer to?

Answer 19

• Appearance of thymic lymphoid follicles containing predominantly B-lymphocytes; thymus is typically normal size
• Better term = thymic follicular hyperplasia

Question 20

Thymic follicular hyperplasia most often occurs in what setting?

Answer 20

Mysathenia Gravis

Question 21

Thymomas are tumors of which cells?

Answer 21

Thymic EPITHELIAL cells usually set against background of non-neoplastic T cells (known as thymocytes)

Question 22

Majority of thymomas arise in which location?

Answer 22

Anterosuperior mediastinum

Question 23

What are some of the presenting sx’s and associated disorders with Thymomas?

Answer 23

• Common sx’s due to impingement on mediastinal structures
• Some present in pt’s with Myasthenia Gravis
• Associated neoplastic disorders: hypogammaglobulinemia, pure red cell aplasia, Graves disease, pernicious anemia, dermatomyositis-polymyositis, and Cushing syndrome

Question 24

By definition, invasive thymomas do what?

Answer 24

Penetrate through capsule into surrounding structures

Question 25

Which variant of thymic carcinoma is most common and what is the next most common?

Answer 25

• Squamous cell carcinoma = most common
• Lymphoepithelioma-like = 2nd most

Question 26

Which variant of thymic carcinoma is associated with EBV?

Answer 26

Lymphoepithelioma-like

Question 27

How does invasive thymoma (type 1) differ from thymic carcinoma (type 2); most often contains which type of epithelial cells?

Answer 27

• Cytologically bland but biologically aggressive
• Cortical-typeepithelial cells =polygonalw/roundtooval, blandnuclei

Question 28

Benign (encapsulated) non-invasive thymomas are most often composed of what type of epithelial cells?

Answer 28

Medullary-type = elongated and spindle-shaped