Follicular Lymphoma

Authors

Colin McCormack, MD (Fellow) and Mark Ewalt, MD (Attending)

Subject: Hematopathology
Clinical History

A developmentally normal and previously healthy 6 year old male presented with unilateral, right testicular enlargement with associated pain. There was no reported fever, weight loss, night sweats, shortness of breath, easy bruising/bleeding or decreased appetite. On physical exam, a firm large testicular mass was noted. A testicular ultrasound revealed a right sided homogenous 3.6 x 2.9 x 2.2 cm intra-testicular mass with near complete parenchymal effacement but without capsular disruption. Laboratory examination revealed normal serum levels of α-fetoprotein, β-human chorionic gonadotropin, and lactate dehydrogenase. A right orchiectomy was then performed.

Figures
orchiectomy, parenchyma, gross image, Cedars-Sinai

Figure 1: Gross image of the bisected orchiectomy showing a unifocal, well circumscribed, firm, tan-white homogenous mass that replaces the entirety of the parenchyma.

nodular, slide, pathology, lymphoid infiltrate

Figure 2: A nodular lymphoid infiltrate with back-to-back follicles replacing the testicular parenchyma is seen. The nodules are of fairly uniform size.

Scattered mitotic figures, pathology, slide, Cedars-Sinai

Figure 3: The follicles contained a mixed population of predominantly large, atypical cells admixed with small cleaved cells. Scattered mitotic figures are also seen. A displaced seminiferous tubules (center right) is also seen in the background.

Immunohistochemistry
slides, pathology, atypical lymphoid cells, express CD20, Cedars-Sinai

Figure 4: The atypical lymphoid cells strongly express CD20 (A), with strong co-expression of BCL6 (B) and dim co-expression of CD10 (C). The proliferation index by Ki-67 is high (50-60%) (D). The atypical cells are uniformly negative for BCL-2 (E). The follicular nature of the nodules is demonstrated by CD21 and shows occasional expansion (F). 

Additional Immunohistochemistry Studies

The neoplastic cells were negative for CD5, MUM1, TdT, CD34, and cMYC.

Molecular and fluorescent in-situ hybridization findings

Clonal immunoglobulin heavy chain (IGH) and kappa light chain (IGK) gene rearrangements were detected by multiplex PCR. There was no detection of t(14:18) IGH/BCL2 or BCL6 rearrangement by fluorescent in-situ hybridization.

Diagnosis

Follicular lymphoma, pediatric type

Discussion

Pediatric type follicular lymphoma is a rare variant of follicular lymphoma that occurs predominantly in children and young adults. It is a neoplastic proliferation of mature B-lymphocytes that presents, most commonly, as localized lymphadenopathy or, less commonly, an extranodal lesion. The cervical lymph nodes and Waldeyer ring are the most commonly described sites of involvement; however extranodal primary involvement of the testicle has also been rarely documented. The majority of patients typically present with localized, early stage (I/II) disease. Patients experience excellent clinical outcomes and, in contrast to the conventional form of the disease, recurrence after treatment is rare.

Pediatric type follicular lymphoma is morphologically indistinguishable from conventional follicular lymphoma. As is seen in conventional form; there is total or subtotal architectural effacement of the background parenchyma by densely packed or "back to back" neoplastic follicles. The neoplastic follicles are often poorly defined, lack polarity, have attenuated or absent mantle zones, and tingible body macrophages are often absent. The follicles are composed of a heterogeneous mixture of centrocytes, centroblasts, histiocytes and follicular dendritic cells. The centroblasts count is often high and, if conventional grading criteria are applied, the majority would be classified as grade 2 or 3. Interfollicular expansion by neoplastic cells with a cleaved, centrocyte-like appearance is common.

The neoplastic follicles show strong expression of B-cell markers and are positive for CD10 and BCL6. In contrast to conventional follicular lymphoma, BCL2 expression is characteristically absent. Similarly, the t(14:18) IGH/BCL2 translocation (observed in 80% of conventional follicular lymphomas) is characteristically absent in this entity although exceptions have been reported.

Molecular genetic studies demonstrate immunoglobulin heavy chain (IGH) gene rearrangements in most cases. A recent study also demonstrated a high prevalence of MAPK pathway mutations and a near absence of mutations in epigenetic modifiers typically seen in conventional follicular lymphoma. These findings strongly support that pediatric type follicular lymphoma is a unique biological entity and may be a useful feature to help distinguish between the two entities.

References

1. Swerdlow, S.H., Campo, E., Harris, N.L., Jaffe, E.S., Pileri, S.A., Stein, H., Thiele, J., Vardiman, J.W. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. IARC. 4th Ed. 2008

2. Louissaint, A., Ackerman, A.M., Dias-Santagata, D., Ferry, J.A., Hochberg, E.P., Huang, M.S., Iafrate, A.J., Lara, D.O., Pinkus, G.S, Salaverria, I., Siddiquee, Z., Siebert, R., Weinstein, H.J., Zukerberg, L.R., Harris, N.L, Hasserjian, R.P. Pediatric-type nodal follicular lymphoma: an indolent clonal proliferation in children and adults with high proliferation index and no BCL2 rearrangement. Blood 2012, 120:2395-2404

3. Oschlies I, Salaverria I, Mahn F, et al. Pediatric follicular lymphoma – a clinico-pathological study of a population-based series of patients treated within the Non-Hodgkin’s Lymphoma - Berlin-Frankfurt-Münster (NHL-BFM) multicenter trials. Haematologica. 2010;95(2):253-259.

4. Liu Q, Salaverria I, Pittaluga S, et al. Follicular Lymphomas in children and young adults: A comparison of the pediatric variant with usual follicular lymphoma. The American Journal of Surgical Pathology. 2013;37(3):333-343

5. Lones MA, Raphael M, McCarthy K, et al. Primary Follicular Lymphoma of the Testis in Children and Adolescents. Journal of Pediatric Hematology/oncology. 2012;34(1):68-71.

6. Louissaint A, Schafernak KT, Geyer JT, et al. Pediatric-type nodal follicular lymphoma: a biologically distinct lymphoma with frequent MAPK pathway mutations. Blood. 2016;128(8):1093-1100.

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