Lymph nodes & spleen, nonlymphoma

• Lesion occurs predominantly in middle aged Asian women and is by definition associated with EBV infection
• F:M = 10:1 to 7:2 (Am J Surg Pathol 2001;25:721, Am J Surg Pathol 2021;45:765)
• Age distribution ranges between 19 and 67 years; mean age of 49 - 58 years (Am J Surg Pathol 2023;47:476, Am J Surg Pathol 2021;45:765, Am J Surg Pathol 2001;25:721)

• Spleen is the most frequent site of involvement, followed by the liver (Am J Surg Pathol 2023;47:476, Am J Surg Pathol 2021;45:765, Am J Surg Pathol 2001;25:721)
• Rare reports in the gastrointestinal (GI) tract and the lungs (Hum Pathol 2015;46:1956, Case Rep Pathol 2019:2019:2648123, Am J Surg Pathol 2023;47:476)
• Nodal IPT cases are excluded; in these cases, EBV is consistently absent in the mesenchymal component (Hum Pathol 2015;46:1956)

• Neoplastic cells are positive for EBV encoded small RNA (EBER)
• Frequent association with EBV genotype A, f variant and with a 30 base pair deletion in exon 3 of the LMP1 gene, demonstrating the presence of a clonal EBV genome (Histopathology 2016;69:883)
  • This implies that EBV plays a role in the etiology of these lesions

• Clinical, laboratory and imaging findings are largely nonspecific
• Endoscopy shows a polypoid mass in cases involving the GI tract (Hum Pathol 2015;46:1956)
• Diagnosis requires histopathological demonstration of characteristic morphology, immunophenotype and EBER positivity by the WHO criteria; these are best evaluated on excisional specimens, including splenectomies

• Solitary, well defined hypodense mass in the affected organ (J Comput Assist Tomogr 2018;42:399)

Images hosted on other servers:

• EBV positive FDC / FRC is an indolent tumor with a propensity for local recurrences in later stages of the disease
• Location seems to be important for the prognosis, with splenic cases showing fewer recurrences than cases in the liver (Int J Clin Exp Pathol 2014;7:2421, Am J Surg Pathol 2001;25:721)
• Distant metastases are rare and have been reported in the lungs and the spine
• Overall mortality rate is 10% for liver cases
• Colonic cases do not seem to recur and can be cured by complete excision (Hum Pathol 2015;46:1956)

Contributed by Elaine S. Jaffe, M.D.


Images hosted on other servers:

• Neoplastic cells are spindled to oval, with vesicular chromatin, a small, central nucleolus and indistinct cytoplasmic borders
• Binucleate cells with a kissing nuclei appearance can be noted in cases with FDC differentiation
• Neoplastic cells form loose fascicles with a storiform appearance
• Rich inflammatory background composed of small lymphocytes, plasma cells and histiocytes; eosinophils can be present (Hum Pathol 1995;26:1093, Am J Surg Pathol 2001;25:721)
• In some cases, the inflammatory component can obscure the sparsely distributed neoplastic cells
• Cytologic atypia is variable; it can range from subtle, with cells showing delicate nuclear membranes, to prominent with Hodgkin / Reed-Sternberg (HRS)-like cells (Am J Surg Pathol 2001;25:721)
• Necrosis can be seen and it has not been consistently associated with more aggressive behavior (Am J Surg Pathol 2001;25:721, Histopathology 2016;69:883, Am J Surg Pathol 2021;45:765)
• Cases referred to as having a hemangioma-like appearance due to the prominence of blood vessel wall hyaline and fibrinoid degeneration have been reported (Am J Surg Pathol 2023;47:476)

Contributed by Elaine S. Jaffe, M.D., Shunyou Gong, M.D., Ph.D. and João Víctor Alves de Castro, M.D.

• Fine needle aspiration biopsy smears, touch imprints and scrape preparations show spindle cells with vesicular, atypical nuclei and delicate cytoplasmic processes distributed singly or in syncytial clusters (Diagn Cytopathol 2008;36:42)
• Nuclear grooves and prominent nucleoli can be seen
• Cellularity ranges from hypo to hypercellular smears
• Background is polymorphic and is rich in lymphocytes, plasma cells and histiocytes; can be hemorrhagic or necrotic
• Immunohistochemistry is mandatory for the diagnosis (see Positive stains)

Images hosted on other servers:

• FDC differentiation is demonstrated by at least a subset of cells positive for one or more markers
  • CD21
  • CD23
  • CD35
  • D2-40
  • Clusterin
  • CNA.42
  • CXCL13
  • SSTR2
• FRC differentiation can be suggested by positivity for smooth muscle actin (SMA)
• Cases with FRC differentiation may or may not be positive for FDC markers
• EBER positivity in the spindle cells is required for the diagnosis
  • EBV latency pattern is not consistently reported but latent membrane protein 1 (LMP1) is positive in 72 - 90% of cases evaluated (Int J Clin Exp Pathol 2014;7:2421, Histopathology 2016;69:883)
• IgG4 positive plasma cells can be present (Am J Surg Pathol 2023;47:476)

Contributed by João Víctor Alves de Castro, M.D. and Elaine S. Jaffe, M.D.

Epstein-Barr virus (EBV) positive inflammatory follicular dendritic cell / fibroblastic reticular cell tumor (ICC, 2022) / EBV positive inflammatory follicular dendritic cell sarcoma (WHO, 5th edition), previously referred to as EBV positive inflammatory pseudotumor (IPT), has been separated from EBV negative lesions that might also be termed IPT. Which of the following is compatible with the diagnosis of EBV positive FDC / FRC?

1. Inflammatory background usually lacks plasma cells
2. Lesion should be nodal in presentation, infrequently involving the spleen or liver
3. Negative results for LMP1
4. Neoplastic cells should have a distinct immunophenotype compatible with both follicular dendritic cell and fibroblastic reticular cell differentiation
5. This lesion has a good prognosis, differing from the aggressive FDC sarcoma (EBV negative)

E. This lesion has a good prognosis, differing from the aggressive FDC sarcoma (EBV negative). EBV positive inflammatory FDC / FRC tumor (ICC, 2022) / sarcoma (WHO, 5th edition) is an indolent neoplasm, in contrast to the aggressive FDC sarcoma. Answer B is incorrect because the lesion should be extranodal. Answer C is incorrect because EBV positivity is an essential criterion usually detected by EBER, but LMP1 can also be detected in many cases. Answer D is incorrect because the immunophenotype is highly variable and can be of either FDC or FRC derivation. Answer A is incorrect because the inflammatory background is important for the diagnosis and usually has prominent plasma cells.

Comment Here

Reference: EBV positive inflammatory follicular dendritic cell / fibroblastic reticular cell tumor