Lymph nodes & spleen, nonlymphoma

Contributed by Kathy Smith, PA

• 4 architectural patterns of reactive hyperplasia are described, depending on the etiology: follicular / nodular, sinus histiocytosis, interfollicular / mixed and diffuse
  • Follicular hyperplasia (most common reactive pattern)
    • Enlarged follicles, varying in size and shape, may coalesce and display different configurations
    • Prominent germinal center and mantle zone
    • Germinal centers show mixed small and large lymphocytes, centrocytes and centroblasts
    • Centroblasts polarize to the medial pole / medullary side forming the darker zone and centrocytes accumulate at the peripheral pole / capsular side forming the lighter zone (Immunity 2016;45:471)
    • Centroblasts are 3 - 4 times larger than the inactivated lymphocytes and show a narrow rim of basophilic cytoplasm and large, round to oval vesicular nuclei with 1 - 3 prominent peripheral nucleoli
    • Mitotic figures are frequent
    • Centrocytes are smaller lymphocytes with scant cytoplasm, cleaved nuclei, clumped chromatin and small or absent nucleoli
    • Numerous tingible body macrophages are a characteristic feature of follicular hyperplasia (Semin Diagn Pathol 2018;35:4, Am J Surg Pathol 1987;11:866)
    • Other cells: plasma cells, T cells and follicular dendritic cells
    • PD-1+ T cells (T follicular helper cells) are seen predominantly at the periphery of the germinal center (Ann Diagn Pathol 2020;44:151421)
    • Mantle zone: around the light zone, small lymphocytes
    • Interfollicular areas may show rare transformed cells (immunoblasts), small lymphocytes, plasma cells and high endothelial venules
    • Monocytoid B cell proliferation may be seen in follicular hyperplasia around cortical sinuses (Pathol Res Pract 1998;194:559)
  • Sinus histiocytosis
    • Expansion of sinuses by histiocytes
    • Common pattern in lymph nodes draining tumor (Br J Surg 1983;70:317)
  • Interfollicular / mixed patterns
    • Paracortical hyperplasia: seen usually in viral infections, nodes draining tumors and autoimmune disorders (Pathol Res Pract 2001;197:237, Hum Pathol 1975;6:363, APMIS 2001;109:419)
    • Mixed small lymphocytes and immunoblasts, with increased vascularity and interdigitating dendritic cells
    • Granulomatous lymphadenitis: necrotizing, nonnecrotizing or suppurative granulomas depending on the etiology (Rev Infect Dis 1986;8:322)
  • Diffuse
    • Architecture may be effaced
    • Diffuse proliferation of mixed small lymphocytes, immunoblasts and plasma cells (APMIS 2001;109:419)
    • Immunoblasts may rarely mimic Hodgkin / Reed-Sternberg cells
• Acute lymphadenitis
  • Sinus dilatation followed by accumulation of neutrophils, vascular dilatation and edema of the capsule
  • Suppurative or necrotizing inflammation may be seen depending on the etiology (Semin Pediatr Surg 2006;15:99)
• Chronic lymphadenitis
  • Follicular hyperplasia, prominence of postcapillary venules, increased number of immunoblasts, fibrosis, plasma cells and histiocytes
  • Capsule may be inflamed or fibrotic (Semin Pediatr Surg 2006;15:99)

Contributed by Jayalakshmi Balakrishna, M.D.

Contributed by Jayalakshmi Balakrishna, M.D.

Contributed by Jayalakshmi Balakrishna, M.D.

• Lymph node, left cervical, needle core biopsy:
  • Reactive lymphoid hyperplasia and no morphologic or immunophenotypic evidence of a lymphoproliferative disorder

If a biopsy were performed, which morphologic feature would best differentiate an EBV+ classic Hodgkin lymphoma from an acute EBV lymphadenitis?

1. Cytologic atypia in CD30+ cells
2. Lack of detection of EBV protein EBNA2
3. Paracortical expansion
4. Positivity by CISH for EBV encoded RNA (EBER)

A. Cytologic atypia in CD30+ cells. Malignant processes involving the lymph node can best be recognized by architectural distortion and cytologic atypia. Hodgkin / Reed-Sternberg cells in classic Hodgkin lymphoma will show complex nuclear features and express CD30, CD15 (often) and dim PAX5. When EBV associated, they will express EBER and EBV LMP1. Answer B is incorrect because Hodgkin / Reed-Sternberg cells may express EBER and LMP1 but are always negative for EBNA2. EBNA2 may be expressed in EBV associated lymphadenitis but is not always present. Answer D is incorrect because EBER can be expressed (although with different patterns) in EBV+ lymphadenitis as well as EBV+ classic Hodgkin lymphoma. Answer C is incorrect because paracortical expansion can be seen in both reactive conditions and lymphoma. EBV+ lymphadenitis generally shows a paracortical expansion.

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Reference: Reactive lymphadenopathy

A 10 year old girl presents with bilateral cervical lymph node enlargement. Her parents state that she has had a fever and throat pain for the past few days. On examination, she is found to have multiple enlarged bilateral cervical lymph nodes. The above image shows a low power view of the cervical lymph node biopsy (H&E, 10x). What is the most likely diagnosis based on the H&E image?

1. Burkitt lymphoma
2. Follicular hyperplasia
3. Follicular lymphoma
4. Paracortical expansion

B. Follicular hyperplasia. The presence of hyperplastic secondary follicles with prominent germinal centers, which show polarization and tingible body macrophages and mantle zone, is favorable for reactive follicular hyperplasia. Answer C is incorrect because follicular lymphoma shows effaced architecture with back to back follicles, absence of polarization and tingible body macrophages; it also lacks well defined mantle zones. Answer A is incorrect because Burkitt lymphoma is a diffuse proliferation of medium sized atypical lymphoid cells with blastoid morphology and conspicuous 1 - 3 nucleoli. Answer D is incorrect because paracortical hyperplasia is the expansion of interfollicular areas with mixed small lymphocytes, immunoblasts, vessels and interdigitating dendritic cells.

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Reference: Reactive lymphadenopathy