© Clinical Chemistry

Infectious Lymphadenopathies

Teresa Scordino MD

University of Oklahoma Health Sciences Center

DOI: 10.15428/CCTC.2018.288654

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Patterns of lymphoid hyperplasia

• Follicular pattern- Follicular hyperplasia

- Syphilis

- HIV lymphadenopathy

- Castleman disease

- Progressive transformation of

germinal centers

• Sinus pattern- Sinus histiocytosis

- Rosai Dorfman disease

- Hemophagocytic syndrome

• Diffuse pattern- Some cases of HSV, EBV

• Paracortical / mixed pattern- EBV lymphadenitis

- HSV lymphadenitis

- Granulomatous lymphadenitis

- Dermatopathic lymphadenopathy

- Drug reaction

- Toxoplasmosis

• Necrosis- HSV

- Cat scratch disease

- Kikuchi Fujimoto disease

- Lupus lymphadenitis

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• Acute phase

o Neutrophilic infiltrate

o Microabscesses → may coalesce into larger abscesses

• Later stages

o Chronic inflammation

o Histiocytes

Bacterial lymphadenitis - general

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• Numerous causeso Infection

– Tuberculosis and other mycobacteria

– Leishmania

– Fungal infection

– Cat scratch disease

– Lymphogranuloma venereum

o Noninfectious syndromes (sarcoidosis)

o Foreign material

o Malignancy

– Classical Hodgkin lymphoma, T cell lymphomas, and other malignancies

Granulomatous lymphadenitis

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• Histoplasma capsulatum

o Granulomatous inflammation, often necrotizing

o 2-4 m, narrow-based budding yeast

• Cryptococcus neoformans

o Granulomatous inflammation

o Clear spaces may be visible around organisms

• Coccidioides immitis

o Granulomatous inflammation

o Large spherules containing small endospores

Fungal lymphadenitis

Histoplasma, GMS stain

Coccidioides immitisPhoto courtesy of Kristian Schafernak

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Mycobacterium tuberculosis lymphadenitis

• Lymph nodes are the second most commonly involved site

• Necrotizing granulomas

M. tuberculosisPhoto courtesy of Kristian Schafernak

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Atypical Mycobacterial lymphadenitis

• Atypical mycobacteria• M. avium, M. marinum,

M. kansasii

• Necrotizing and non-necrotizing granulomas

• Foamy macrophages

M. avium, AFB stain

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• Cat scratch disease

• Lymphadenopathy 1-3 weeks after exposure

• Early: small abscesses, follicular hyperplasia

• Late: large stellate necrotizing granulomas -abscesses surrounded by palisading histiocytes

• Warthin-Starry, IHC may reveal organisms

• PCR, serology

Bartonella henselae lymphadenitis

Palisading

histiocytes

Neutrophils

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• Chlamydia trachomatis serovars L1-L3

• May be preceded by genital ulcer

• Unilateral tender enlargement of regional

nodes

• Morphologically similar to cat scratch

lymphadenitis

Lymphogranuloma venereum lymphadenitis

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• Immunosuppressed patients

• Bartonella infection with associated vascular proliferation

• Skin lesions often present

• Nodular proliferation of small vessels

• Mild endothelial atypia

• Extravasated RBCs

• Granular material visible on H&E (arrow)

Bacillary angiomatosis

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• Primary infection: typically involves nodes near site of primary infection (inguinal > cervical)

• Secondary infection: generalized lymphadenopathy

• Follicular hyperplasia

• Paracortical expansion with small lymphocytes, plasma cells, immunoblasts

• Thickening of capsule

• Perivascular lymphoplasmacytic infiltrate

Syphilitic lymphadenitis

Plasma cells

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Toxoplasma lymphadenitis

Reactive germinal center

Monocytoid B cells

Epithelioid histiocytes

Epithelioid histiocytes

encroaching on GC

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• Lymph node findings vary with stage of disease

• Pattern A

o Follicular hyperplasia

o Monocytoid B cells may be present

• Pattern C

o Small, regressed follicles

o Increased interfollicular plasma cells

• Pattern B

o Intermediate between patterns A and C

HIV lymphadenitis

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• Frequently involves cervical lymph nodes

• Follicular hyperplasia

• Paracortical expansion

o Variably-sized lymphocytes, immunoblasts,

plasma cells

o Sheets of immunoblasts, RS-like cells may be

seen

• Necrosis may be present

Epstein-Barr virus lymphadenitis

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Epstein-Barr virus lymphadenitis

Immunoblasts

Necrosis

Reed-Sternberg-like cell

EBER

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• Hyperplastic follicles may be present

• Paracortical expansion with lymphocytes, plasma cells, immunoblasts

• Diffuse areas of necrosis with karyorrhectic debris, neutrophils

• Viral cytopathic effect

• Association with CLL/SLL

Herpes simplex lymphadenitis

HSV IHC

Necrosis

Viral cytopathic

effect

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• Infection is a common cause of

lymphadenopathy

• Familiarity with the features of infectious

lymphadenopathies is important

o Helps prevent misdiagnosis of malignancy

o Gives the clinician a specific diagnosis

o Helps direct appropriate further testing and

management

Conclusions

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References

1. Asano S. Granulomatous lymphadenitis. J Clin Exp Hematopathol 2012;52(1):1-16.

2. Lin MH, Kuo TT. Specificity of the histopathological triad for the diagnosis of toxoplasmic lymphadenitis: polymerase chain reaction study. Pathol Int. 2001;51(8):619-23.

3. Loissant A, Ferry JA, Soupir CP, Hasserjian RP, Harris NL, Zukerberg LR. Infectious mononucleosis mimicking lymphoma: distinguishing morphological and immunophenotypicfeatures. Mod Pathol 25(8):1149-59 2012

4. Medeiros LJ, Lin P, Miranda RN. Infectious mononucleosis. In: Diagnostic Pathology: Lymph Nodes and Extranodal Lymphomas, Second Edition. Elsevier, PA 2018: 78-83.

5. Miranda RN, Khoury JD, Medeiros LJ. Cat scratch lymphadenitis. In: Atlas of Lymph Node Pathology, Atlas of Anatomic Pathology, Springer, NY, 2013: 35-36.

6. Miranda RN, Khoury JD, Medeiros LJ. Fungal lymphadenitis: Histoplasma, Cryptococcus, and Coccidioides. In: Atlas of Lymph Node Pathology, Atlas of Anatomic Pathology, Springer, NY, 2013: 53-57.

7. Miranda RN, Muzzafar T, Medeiros LJ. Human immunodeficiency virus lymphadentitis. In: Diagnostic Pathology: Lymph Nodes and Extranodal Lymphomas, Second Edition. Elsevier, PA 2018: 122-131.

8. Pittaluga, S. Viral-associated lymphoid proliferations. Semin Diagn Pathol. 2013 May ; 30(2): 130–136.

9. Salem A, Loghavi S, Khoury JD, Agbay RL, et al. Herpes simplex infection simulating Richter transformation: a series of four cases and review of the literature. Histopathology 2017;70(5):821-831

10. Zangwill KM. Cat scratch disease and other Bartonella infections. Adv Exp Med Biol2013;764:159-66

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Disclosures/Potential Conflicts of Interest

Upon Pearl submission, the presenter completed the Clinical Chemistry

disclosure form. Disclosures and/or potential conflicts of interest:

▪ Employment or Leadership: No disclosures

▪ Consultant or Advisory Role: No disclosures

▪ Stock Ownership: No disclosures

▪ Honoraria: No disclosures

▪ Research Funding: No disclosures

▪ Expert Testimony: No disclosures

▪ Patents: No disclosures

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