Inflammatory Pseudotumor-like Follicular Dendritic Cell Tumor

Roberto N. Miranda, MD

Key Facts

Terminology

Inflammatory pseudotumor-like follicular dendritic cell tumor (IPT-FDCT)
Considered variant of follicular dendritic cell sarcoma
Classification is controversial

Clinical Issues

Marked female predominance
Good prognosis; no deaths attributable to IPT-FDCT of spleen
IPT-FDCT affecting liver can be recurrent and metastatic in rare cases

Microscopic Pathology

Well-demarcated single mass with occasional incomplete fibrous capsule
Loosely aggregated or dispersed oval or spindle cells admixed with abundant inflammatory cells

Ancillary Tests

Usual reactivity with follicular dendritic cell markers
Epstein-Barr virus encoded RNA (EBER)(+) in spindle cells in 40% of cases
Cases that are EBV(+) show that viral genome is monoclonal

Top Differential Diagnoses

Splenic inflammatory pseudotumor
Follicular dendritic cell sarcoma
Inflammatory myofibroblastic tumor
Sclerosing angiomatoid nodular transformation of red pulp

Inflammatory pseudotumor-like follicular dendritic cell tumor displays cellular

and sclerotic

areas. (Courtesy M. Vasef, MD.)

Inflammatory pseudotumor-like follicular dendritic cell tumor shows extensive necrosis

, which is a feature that may mislead to a diagnosis of malignancy when detected by imaging studies.

TERMINOLOGY

Abbreviations

Inflammatory pseudotumor-like follicular dendritic cell tumor (IPT-FDCT)

Synonyms

Terms inflammatory pseudotumor and inflammatory myofibroblastic tumor have been used as synonyms in the literature
- This is confusing and may be incorrect
- In this chapter these entities are distinguished

Definitions

IPT-FDCT is considered a variant of follicular dendritic cell sarcoma
Classification is controversial since several entities were previously lumped into category of splenic IPT
- IPT-FDCT
  - True neoplasm of low malignant potential
  - Frequent association with Epstein-Barr virus (EBV)
  - Tends to involve spleen &/or liver
  - May overlap with EBV(+) cases without follicular dendritic cell markers
- ALK(+) inflammatory myofibroblastic tumor (IMT)
  - Most often involves soft tissues of children and young adults
  - ˜ 50% of tumors have rearrangements at 2p23 involving anaplastic lymphoma kinase (ALK)
- Splenic inflammatory pseudotumor (IPT)
  - Reactive process composed of admixed bland spindle cells and inflammatory cells
  - Probably results from multiple etiologies, including infections and repair
  - Benign lesions that do not recur after surgical excision

ETIOLOGY/PATHOGENESIS

Infectious Agents

Etiology is unknown
Strong association with Epstein-Barr virus
- Epstein-Barr virus is monoclonal when assessed by EBV DNA terminal repeat regions

Cell of Origin

Spindled cells express 1 or more follicular dendritic cell markers
Spindled cells also can express focally smooth muscle actin or S100 protein
Cell of origin may be mesenchymal cell with differentiation along fibroblastic, myofibroblastic, or follicular dendritic cell lineages

CLINICAL ISSUES

Epidemiology

Incidence
- Uncommon; ˜ 1% of splenic tumors
- Rare when compared with IPT at other sites of body
Age
- Median: 44 years (range: 19-87 years)
  - Rare in children
Gender
- Female predominance

Site

Appears in spleen as single lesion

Presentation

Affected patients are immunocompetent
Fever and weight loss in approximately 1/2 of patients
Epigastric or left flank pain in subset of patients
- Splenomegaly may be noted in some cases
Can be incidental finding in asymptomatic patients
- Lesion in spleen detected by radiologic imaging performed for other diseases
- Imaging studies can demonstrate significant tumor growth in patients followed with less than 1 year intervals

Laboratory Tests

Usually unremarkable when not associated with other disease

Natural History

Cases of splenic IPT-FDCT appear to be closely related to liver IPT-FDCT
- Histologically similar
- Share association with EBV
More clinical information and follow-up are available for liver IPT-FDCT
- Recurrences and metastases have been reported
- Rare transformation of IPT-FDCT into overt follicular dendritic cell sarcoma

Treatment

Patients usually are diagnosed/treated with splenectomy
- Due to rarity and nonspecific CT or MR imaging, these tumors are not diagnosed preoperatively
Symptoms and any laboratory abnormalities disappear after tumor resection

Prognosis

Good; no deaths attributable to IPT-FDCT of spleen

IMAGE FINDINGS

CT Findings

Discrete, single splenic mass and occasional splenomegaly
Lymphadenopathy is unusual

MACROSCOPIC FEATURES

General Features

Spleen weight: Ranges from 140-1,030 g
Well-circumscribed single mass
- Cut surface is tan, gray, and firm; bulges in cross section
  - May have focal necrosis
- Size: Ranges from 3-22 cm

MICROSCOPIC PATHOLOGY

Histologic Features

Well-demarcated tumor with occasional incomplete fibrous capsule
Loosely aggregated or dispersed oval or spindle cells admixed with abundant inflammatory cells
- Spindled cells with moderate amount of pale to faintly eosinophilic cytoplasm
  - Oval vesicular nuclei with minimal atypia and distinct small nucleoli
- Occasional small fascicles or focal storiform pattern
- Rare mitotic figures
- Occasional large cells with abundant cytoplasm and pleomorphic nuclei
Mixed inflammatory infiltrate of plasma cells, lymphocytes, and histiocytes
- Lymphocytes are usually small admixed with occasional immunoblasts
- Mature plasma cells with occasional Russell bodies
Other microscopic features
- Focal necrosis with neutrophilic infiltrate
- Histiocytes &/or eosinophils can be numerous

ANCILLARY TESTS

Immunohistochemistry

Spindled cells
- Usually focal and weak reactivity with 1 or more follicular dendritic cell markers
  - CD21, CD35, CNA.42 (more frequent), and CD23 (less frequent)
  - More studies needed to establish frequency, pattern, intensity of expression of these markers
- Vimentin(+), focal CD68(+), and focal smooth muscle actin(+/-)
- Occasionally S100 protein ([+] focal)
- EBV LMP1 occasionally (+)
- Negative for CD15, CD30, CD34, EMA, and cytokeratin
- HMB-45(-), ALK-1(-), HHV8(-)
Lymphocytes and plasma cells
- T cells are usually more abundant than B cells
- B cells and plasma cells are polytypic

In Situ Hybridization

Epstein-Barr virus encoded RNA (EBER)(+) in spindle cells in 40% of cases
- Surrounding spleen is EBER(-) or degree of positive cells is significantly lower

Molecular Genetics