Non-neoplastic Disorders

of the

Lymphoid System
T. Utoro Department of Pathology GMUSM

Lymph nodes
Consist of organized collections of lymphoid tissue, located along the lymphatic vessels Aggregates of lymphoid tissue are also found along the course of GI tract from Waldeyer ring (oropharynx & nasopharynx), to Peyer patches (terminal ileum) MALT, bronchial tree (BALT) Typically grayish white and ovoid or bean-shaped, they vary from 2 mm to 2 cm in diameter A fibrous capsule and radiating trabeculae provide a supporting structure, and delicate reticular network contribute internal support Architecturally exhibit outer cortex and inner medulla. The cortex contains defined B-cell and T-cell domains

Structure of Normal Lymphnode

Normal germinal center

Mantle zone

Showing distinct zoning, the lower half containing closely packed and rapidly dividing centroblast.

Normal germinal center

Stained with monoclonal antibody to proliferating cells (Ki-67).

Numerous dividing cells (brown nuclei) are seen in the lower , centroblast rich region of the germinal center.

Normal germinal center

High power view of phagocytic/tingible body macrophage (arrowed) engulfing apoptotic lymphoid cells. These are concentrated in the most proliferative part of the germinal center.

Non-neoplastic Disorders of the Lymph nodes

Reactive (inflammatory) proliferation Acute non-specific lymphadenitis Chronic non-specific lymphadenitis - Follicular hyperplasia - Paracortical lymphoid hyperplasia - Sinus histiocytosis Chronic specific lymphadenitis - Granulomatous lymphadenitis - Necrotizing lymphadenitis
- Lymphogranuloma venereum - Cat-scratch Disease

Reactive (inflammatory) proliferation

Acute non-specific lymphadenitis

Lymph nodes undergo reactive changes whenever they are challenged by microbiologic agents or others Macroscopically the lymph nodes become swollen, grayred and engorged Histologically there is prominence of the lymphoid follicle with large germinal centers containing numerous mitotic figures Pyogenic organism suppurative inflammation neutrophil Clinically leukocytosis

Reactive (inflammatory) proliferation

Acute non-specific lymphadenitis

Reactive changes in neutrophil: containing coarse purple cytoplasmic Granules (toxic granulation) Arrow: blue cytoplasmic patches of dilated endoplasmic reticulum (Dohle bodies)

Reactive (inflammatory) proliferation

Leukocytosis

Reactive (inflammatory) proliferation

Leukocytosis

Lymphocytosis Lymphocytopenia:

Lymphocytosis

Peripheral blood lymphocytosis is defined as an increase in the absolute peripheral blood lymphocyte count above the normal range (adults: 4000 l, children: 7000 l, infants: 9000 l) Reflects infections or lymphoproliferative condition Plasmacytosis is common in end-stage multiple myeloma

Lymphocytosis lymphocytopenia:

Lymphocytopenia

Decrease in the absolute peripheral blood lymphocyte count to less than normal range (adults: 1500 l, children: 3000 l) Mechanism: decreased production, increased destruction, and loss of lymphocytes

REACTIVE (INFLAMMATORY) PROLIFERATION

Chronic non-specific lymphadenitis

FOLLICULAR HYPERPLASIA PARACORTICAL LYMPHOID HYPERPLASIA SINUS HISTIOCYTOSIS

REACTIVE (INFLAMMATORY) PROLIFERATION

Chronic non-specific lymphadenitis

FOLLICULAR HYPERPLASIA

Reactive hyperplasia of lymph nodes is a response to infections, inflammation, or tumors Types:

Hyperplasia of secondary follicles (germinal centers) and plasmacytosis of the medullary cord indicate B-lymphocyte immunoreactivity Hyperplasia of the deep cortex and paracortex (interfollicular or diffuse hyperplasia) is characteristic of T-lymphocyte immunoractivity

Patterns of Benign Reactive Hyperplasia

B-cell immunoreactivity

T-cell immunoreactivity

Reactive proliferation of the mononuclearphagocyte system

Complex immune reactions

Common infectious disease

Granulomatous inflammation

Follicular hyperplasia
Castleman disease (Angiofollicular lymph node hyperplasia)
- Hyaline-vascular angiofollicular lymph node hyperplasia (90%) - Plasma cell angiofollicular lymph node hyperplasia (10%)

AIDS lymphadenopathy
- marked follicular hyperplasia, with a distinctive loss of mantle zone - Infiltration of follicle by clusters of small lymphocytes - foci of interfollicular hemorrhage (follicle lysis) - focal perisinusoidal, monocytoid, B-cell hyperplasia

Follicular hyperplasia

Mantle zone

Dark zone of the follicle

Several mitotic figures and numerous macrophages containing phagocytosed apoptotic cells (tingible bodies)

FOLLICULAR HYPERPLASIA

Hyperplastic lymphnode with prominent follicle containing numerous macrophages with pale cytoplasm.

Compared with follicular neoplasia

Chronic non-specific lymphadenitis

Reactive Inter-follicular Hyperplasia Common type hyperplasia in infectious mononucleosis and Kikuchi disease Is also common finding in viral infection (inf.monnucleosis, varicella-herpes zoster infection, measles, CytoMegaloVirus lymphadenitis) or in immunological reaction

Chronic non-specific lymphadenitis

Reactive Inter-follicular Hyperplasia

Small lymphocytes, variably activated lymphocytes, immunoblast, scattered macrophages

Infectious mononucleosis
Benign, self limited disorder caused by EBV, and frequently occur in young adult Characterized by circulating atypical lymphocytes (reactive CD8+ T-lymphocyte) EBV has affinity for B lymphocytes: healthy person infectious mononucleosis, immunosuppressed person Burkitt lymphoma Clinically characterized by prominent sore-throat, fever and generalized lymphadenopathy, and often by hepatosplenomegali The spleen is especially susceptible to traumatic rupture

Follicular hyperplasia

HISTIOCYTIC NECROTIZING LYMPHADENITIS

Kikuchi disease
Unusual lymphadenitis in young women Most commonly involves the cervical lymph nodes Prominent karyorrhexis and cytoplasmic debris characteristic Granulocytes are absent Usually self-limited and resolved within 3 to 4 months Viral etiology is suspected

Chronic non-specific lymphadenitis:

PARACORTICAL LYMPHOID HYPERPASIA

Involve deep cortex or paracortex Two important entities: dermatopathic lymphadenopathy - severe eczema - psoriasis - mycosis fungoides infectious mononucleosis

Chronic non-specific lymphadenitis:

SINUS HISTIOCYTOSIS
Refers to an increase of tissue macrophages (histiocyte) of the subcapsular and trabecular sinuses of the lymph nodes Common finding in lymph nodes draining site of cancer, and less commonly in inflammatory and infectious foci Sinus histiocytosis may follows massive lymphadenopathy SHML ( sinus histiocytosis with massive lymphadenopathy) also known as Rosai-Dorfman disease (a rare self-limited disease of unknown etiology, characterized by striking, bilateral, painless, cervical lymphadenopathy)

Benign Disorders of mononuclear phagocyte system

A. B. C. D. E.

In benign sinus histiocytosis: nodal sinuses are expanded by bland histiocytes In sinus histiocytosis with massive lymphadenopathy: macrophages contain lymphocytes In dermatopathic lymphadenopathy: contains cytoplasmic lipid & melanin pigment In infection-induced hemophagocytic reticulosis: contains phagocytosed red cells In differentiated histiocytoses: cells are bland with cleaved nucleii

REACTIVE LYMPHADENITIS

Chronic specific lymphadenitis

GRANULOMATOUS LYMPHADENITIS NECROTIZING LYMPHADENITIS

GRANULOMATOUS LYMPHADENITIS
MYCOBACTERIAL INFECTION SARCOIDOSIS CROHNS DISEASE TOXOPLASMIC LYMPHADENITIS

Tuberculous Lymphadenitis

Refer to block respiratory diseases

Sarcoidosis
A granulomatous disorder of unknown etiology The granuloma of the sarcoidosis are the classic epitheloid cell type, without caseation necrosis Mostly affect the lungs

Crohn Disease
A transmural, chronic inflammatory disease that may affect any part of the digestive part but occurs principally in the distal small intestine Included in IBD Microscopic hallmark: transmural nodular aggregates, with discrete non-caseating granulomas

Toxoplasmic lymphadenitis

Caused by Toxoplasma gondii, mostly asymptomatic Follicular hyperplasia with epitheloid granulomas adjacent to germinal centers. There is also perifollicular proliferation of uniform B-cells, termed monocytoid B-cells.

NECROTIZING LYMPHADENITIS Lymphogranuloma Venereum Cat Scratch Disease

NECROTIZING LYMPHADENITIS

Lymphogranuloma venereum

Sexually transmitted chlamydial disease, most commonly affects the groin nodes Lymphatic involvement fibrosis, scaring, and strictures of anus and rectum Etiology: C.trachomatis

NECROTIZING LYMPHADENITIS

Catch scratch disease

Follow a scratch or bite from an infected cat Days to weeks later tender lymphadenopathy I cervical or axillary region Etiology: Afipia felis, a pleomorphic coccobacillus Microscopically: stellate abscess

NECROTIZING LYMPHADENITIS

Cat scratch disease

Stellate-like central abscess formation surrounded by pallisaded histiocytes.