August 2017 Case

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

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.

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

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.

Follicular lymphoma, pediatric type

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.

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