Reactive lymphadenopathies

Question 1

Describe four “patterns” of lymph node architecture in which all reactive lymphadenopathies can be placed.

Answer 1

Follicular/Nodular

Predominantly sinus

Interfollicular/Mixed

Diffuse

Question 2

Describe the morphologic features of reactive follicular hyperplasia.

Answer 2

Increase in size and number of secondary follicles with usual dark and light zones.

Germinal centers are typically CD10+, BCL2-, BCL6+.

Question 3

How can follicular lymphoma be distinguished from reactive follicular hyperplasia?

Answer 3

In follicular lymphoma, there is aberrant germinal center expression of BCL2 (may not be true of the pediatric type).

Germinal centers also lack tingible body macrophages.

Question 4

Describe the morphologic feature of rheumatoid arthritis (RA) related lymphadenopathy.

Answer 4

May resemble multicentric hyaline vascular Castleman’s disease, with paracortical hyperplasia.

Proliferation of larger atypical immunoblastic cells may resemble Hodgkin lymphoma.

Question 5

Describe the morphologic features of Luetic lymphadenitis.

Answer 5

Follicular hyperplasia with interfollicular plasmacytosis, granulomas, and endarteritis/venulitis.

Can rarely be necrotizing or form an inflammatory pseudotumor.

Question 6

Describe the morphologic features of hyaline vascular Castleman’s disease.

Answer 6

Numerous small/regressive germinal centers surrounded by an expanded onion-skinned mantle zone and hypervascular interfollicular region with lollipop vessels.

Question 7

Describe the clinical manifestations and etiology of hyaline vascular Castleman’s disease.

Answer 7

Usually unicentric enlargement of a lymph node in young adults. Associated with HHV-8/KSV.

Question 8

What reactive conditions should be considered with a lymph nodal proliferation of interfollicular plasma cells?

Answer 8

Syphilis / Luetic lymphadenitis

Castleman’s disease, plasma cell variant

IgG₄-related lymphadenopathy

Question 9

What is progressive transformation of germinal centers (PTGC)? Describe its morphology.

Answer 9

An asymptomatic, usually self-limited lymph node enlargement, usually in young men.

Germinal centers are markedly enlarged with mantle cell immunophenotypes (IgD+).

Question 10

Describe the etiology and morphology of mycobacterial spindle cell tumor.

Answer 10

A histiocytic proliferation usually in HIV+ patients due to mycobacterial infection. To be distinguished from Kaposi’s sarcoma.

Bland spindle cells form fascicles/storiform patterns and stain for CD68. AFB stains organisms.

Question 11

What are some causes of sinus histiocytosis?

Answer 11

Drainage of inflamed or neoplastic sites

Lymphangiography (w/ foamy histiocytes)

Foreign material (giant cell rxn)

Hereditary storage diseases

Question 12

What causes Whipple’s disease? Describe its morphology.

Answer 12

Tropheryma whipplei; resulting in abdominal lymphadenopathy and GI malabsorption.

Sinus histiocytes appear large and finely vacuolated; PAS reveals sickle-shaped organisms.

Question 13

What is vascular transformation of the sinuses (VTS)? Descirbe its morphology.

Answer 13

Expansion and replacement of subcapsular sinuses by thin-walled vessels. Results from chronic obstruction? May be solid, spindled, or plexiform.

Question 14

What are some causes of hemophagocytic lymphohistiocytosis (HLH)?

Answer 14

Primary/Congenital: Multiple mutations including in STS11, PRF1, UNC13D, and STXP2.

Secondary/Acquired: Viral infections, autoimmune disorders, malignancies, NK/T-cell lymphomas (especially primary cutaneous gamma-delta T-cell lymphoma)

Question 15

What are the clinical signs of hemophagocytic lymphohistiocytosis (HLH)?

Answer 15

Fever, organomegaly, skin rash.

Lab results show extreme elevation in ferritin, and hyperlipidemia with red cell anemia.

Question 16

Describe the morphology of hemophagocytic lymphohistiocytosis (HLH).

What should be considered in the differential?

Answer 16

Sinus proliferation of benign histiocytes stuffed with erythrocytes.

Consider Rosai-Dorfman (emperipolesis can mimic), Langerhans cell histiocytosis (CD1a/S100+).

Question 17

Describe the etiology and morphology of dermatopathic lymphadenitis.

Answer 17

Drainage of chronically irritated skin.

Expansion of paracortex with interdigitating dendritic cells (CD1a+, S100+) and variable immunoblasts. Melanopages (CD68, pigmented) may be present.

Question 18

What are some possible causes of granulomatous lymphadenopathy?

Answer 18

Non-necrotizing: Non-specific reaction to malignancy (HL, LPL, PTCL), sarcoidosis and other systemic disease

Necrotizing: Mycobacterial/fungal infection, cat-scratch disease

Question 19

What are the morphologic features of Cat-Scratch disease?

Answer 19

Suppurating granulomas and monocytoid B-cell proliferation.

Question 20

How does IgG₄-related lymphadenopathy appear histologically?

Answer 20

There are actually 5 patterns of architecture; most feature increased plasma cells and positive staining for IgG4.

Question 21

Describe the epidemiology and clinical manifestations of Kimura’s disease.

Answer 21

Mostly affects asian men, manifesting with a head/neck mass with peripheral eosinophilia and elevated IgE.

Question 22

Describe the morphology of Kimura’s disease.

Answer 22

Florid follicular hyperplasia with proteinaceous IgE precipitate, prominent eosinophils, and prominent HEVs.

Question 23

What is the morphologic triad seen in Toxoplasma lymphadenitis?

Answer 23

Prominent follicular hyperplasia

Expansion of monocytoid B cells (sinusoidal/parasinusoidal)

Clusters of epithelioid histiocytes (“microgranulomas”) but no true granulomas.

Question 24

Describe the morphologic features of SLE lymphadenitis.

Answer 24

Non-specific follicular hyperplasia with numerous plasma cells.

Coagulative necrosis is often present, with hematoxylin bodies as a relatively specific feature of SLE.

Question 25

Describe the epidemiology and manifestations of Kikuchi’s lymphadenitis.

Answer 25

Mostly affects asian women.

Presents with cervical lymphadenopathy with fever & leukopenia.