Histiocyte, Spleen and Thymus Pathology Flashcards
Histiocyte Disorders
- Histiocyte pathology encompasses a heterogenous group of disorders ranging from benign, reactive disorders to highly aggressive malignant neoplasms.
- The most common of thes is the Langerhans cell histiocytoses (LCH).
Langerhans Cell
- LCs are produced in the bone marrow and are derived from the monocyte-macrophage lineage.
- LCs are a special type of dendritic cell that picks up antigen in the peripheral tissues and then migrates to lymph nodes where they are powerful activators of T-cells.
- Recent data has shown that the cell of origin for LCH is not a cutaneous LC, but rather a myeloid dendritic cell. For now, however, these disorders are still referred to as Langerhans cell histiocytoses.
Langerhans Cell Histiocytosis
- LCH is a clinicopathologic entity classified according the number of sites involved (single vs multiple) and their location (single organ or multiple organs).
- Older, historical names include Letterer-Siwe, Hand-Schuller-Christian, and eosinophilic granuloma
- These are RARE entities (~5 cases/million population/year) and most cases occur in childhood. The etiology is unknown in most cases.
LCH - Symptoms
•Preferential involvement of:
- Skin (80% of patients)
- Scalp, face, trunk, buttocks, intertriginous areas
- Closely spaced papules with scale and crust
- Bone
- Liver
- Spleen
- Bone marrow
LCH Entities
1) Multifocal System LCH (Letterer - Siwe Disease)
2) Unisystem (umifocal or multifocal)
3) Pulmonary LCH (eosinophilic granuloma of lung)
LCH - Multifocal multisystem (Letterer - Siwe Disease)
o Infants and children <2 years old, occasional adults
o Skin, bone, liver, spleen and bone marrow
o Aggressive course; most patients require chemotherapy
LCH - Unifocal (unifocal or multifocal)
o Unifocal disease:
§ Skeleton (skull, ribs and femur), older children/adults
§ Indolent, may regress spontaneously
o Multifocal disease:
§ Young children
§ Multiple erosive bone lesions
§ Exophthalmos
§ Involvement of the posterior pituitary stalk of the hypothalamus leads to diabetes insipidus (most common endocrine abnormality in LCH)
§ Prognosis depends on sites of involvement; may require systemic chemotherapy
LCH - Pulmonary
o Adult smokers (may regress upon smoking cessation)
§ Reactive, non-clonal process??
o Chronic interstitial lung disease with nodular and cystic lesions
o Nonproductive cough, dyspnea, fever, weight loss
o May be discovered incidentally on CXR
Diabetes in LCH
LCH Histology
- Langerhans cells have abundant cytoplasm and nuclei with linear grooves and minimal atypia; they may be admixed with eosinophils (often prominent), lymphocytes, plasma cells and neutrophils
- Nuclei
- kidney bean shaped
- linear grooves (coffee bean)
- minial atypia
LCH - Electron Microscopy
• Birbeck granule
- Pentalaminar tubule with dilated terminal end
- Contains the protein Langerin
- Birbeck granules, CD1a and langerin play a role in antigen presentation to Tcells
LCH Genetics
- Phenotype: LC express HLA-DR, S100, and CD1a
- Genetic Profile: BRAF V600E mutation positive in ~50% of cases
White Pulp of Spleen
The white pulp is involved in generating immune responses to antigens in the blood, and consists of T and B cells and associated cells surrounding central arteries.
Red Pulp of Spleen
The red pulp consists of splenic sinusoids separated by splenic cords. Splenic sinusoids are made up of spindle-shaped endothelial cells and are the actual filter of the spleen. Blood cells that enter the red pulp must pass through the walls of the splenic sinusoids to re-enter circulation.
Spleen Functions
- Phagocytosis of blood cells (senescent and abnormal), particulate matter and microorganisms. Abnormally shaped or antibody-coated RBCs are phagocytosed by macrophages.
- Antibody production – dendritic cells in the periarteriolar lymphoid sheath (PALS) trap and present antigens to T-cells, leading to activation and proliferation of B and T lymphocytes and antibody-producing plasma cells.
- Hematopoiesis – normal prior to birth; can be seen after birth in response to marrow failure or in myeloproliferative neoplasms
- Sequestration of blood cells – especially RBCs and platelets
Splenomegaly
Splenic enlargement. The major manifestation of disorders of the spleen.
Splenomegaly - White Pulp
Splenomegaly - Red Pulp
SPlenomegaly - Red and White Pulp
Congestive Splenomegaly
•Congestive splenomegaly is caused by chronic venous outflow obstruction, and may be seen in the following conditions:
1) Congestion (systemic or central venous) - causes moderate spleen enlargement
2) Cirrhosis of the liver - main cause of congestive splenomegaly
3) Obstruction of the extrahepatic portal vein or splenic vein
- Morphology: With long-standing congestion, the spleen may become markedly enlarged (1000-5000 gm) and firm.
- Microscopically, there is early congestion but eventually the red pulp becomes fibrotic.
Congenital Anomalies of the Spleen
- Complete absence of the spleen is rare, typically associated with other abnormalities
- Accessory spleen (aka supernumerary spleen, spleniculi)
o Small spherical structures identical to the normal spleen
o Located anywhere in abdominal cavity
o Identified in up to 35% of autopsies
o Important to find in patients undergoing splenectomy for hematologic disease because the accessory spleen may undergo hyperplasia after splenectomy leading to disease recurrence
Hyposplenism - Sickle Cell Disease
•Sickle cell disease: Early on, the spleen is enlarged due to trapping of sickled cells in the sinuses leading to congestion in the red pulp. With time, chronic stasis of RBCs leads to infarction, fibrosis and progressive shrinkage. By adolescence or early adulthood, only a small remnant of fibrotic spleen is present. This process is known as autosplenectomy
Hyposplenism and Asplenia Histology
•A normal spleen removes excess RBC membrane and inclusions. In the absence of a functional spleen, this does not happen and many erythrocytes become target cells and contain nuclear remnants (Howell-Jolly bodies)
Splenic Rupture
- Splenic rupture typically results from trauma. Rarely, splenic rupture occurs without a history of trauma (“spontaneous rupture”) and is usually seen in splenic conditions that cause rapid enlargement of the spleen that causes stretching of the capsule.
- Common predisposing conditions include infectious mononucleosis, malarial infection, and lymphoid neoplasms.
- Chronically enlarged spleens are less susceptible to rupture.
•Hassall’s corpuscles (or thymic corpuscles (bodies)) are structures found in the medulla of the human thymus, formed from eosinophilic type VI epithelial reticular cells arranged concentrically.
Thymic Follicular Hyperplasia
- Characterized by the appearance of B-cell follicles in the thymus.
- Occurs in association with a number of chronic inflammatory and immunological states.
- Most frequently associated with myasthenia gravis, other autoimmune disorders. Other associated conditions include Graves’ disease, SLE, scleroderma, and RA.
What is the pathogenesis of myasthenia gravis?
- Ocular symptoms (>50% of patients)
- Ptosis and/or diplopia
- Bulbar symptoms (15%)
- Dysarthria, dysphagia, fatigable chewing
- Limb weakness (<5%)
Thymoma
- Thymoma is the most common primary neoplasm of the anterior mediastinum in adults; rare in children.
- Age: 30-50 yrs
- Asymptomatic in up to 50%
- Clinical Presentation
- Myasthenia gravis
- Substernal pain, dyspnea, cough, superior vena cava syndrome
- Anemia due to pure red cell aplasia
Thymoma - Histology
- Neoplasm of thymic epithelial cells with variable component of thymocytes
- Histologic classification based on composition of neoplasm
- Epithelial
- Lymphocytic
•Variable cytologic features
-Benign or malignant
•surgical stage (based on invasion of capsule and surrounding tissue)
o Noninvasive thymoma
o Invasive thymoma
o Thymic carcinoma
