Spontaneously Ruptured Spleen Samples in Patients With Infectious Mononucleosis

Analysis of Histology and Lymphoid Subpopulations

Marcos M Siliézar, MD; Catuxa Celerio Muñoz, MD; Jon Danel Solano-Iturri, MD; Laura Ortega-Comunian, MD; Manuela Mollejo, MD; Santiago Montes-Moreno, MD; Miguel A Piris, MD

Disclosures

Am J Clin Pathol. 2018;150(4):310-317. 

In This Article

Results

Clinical Data

Patient age ranged from 15 to 25 years. Two of the patients described previous symptoms suggesting IM. Two of the patients died because of intra-abdominal hemorrhage and hypovolemic shock. Four patients, for whom follow-up data were available, remained alive and well after 3 to 240 months follow-up Table 2.

Spleen weight ranged from 276 to 460 g. A diagnosis of IM was established after clinical and serologic study, before or after splenectomy.

Description of the Histology

Splenic infarcts were present in all cases, together with subcapsular and intraparenchymal lacerations. Viable areas of the spleen had a homogeneous macroscopic appearance, without nodules. The number of studied blocks varied between hospitals; generally, we received one paraffin block from the spleen and additional blocks from any macroscopic change and hilar lymph nodes, when excised. Histologic study disclosed red pulp expansion with partial loss of the white pulp, a major finding in all cases. Focal geographic necrosis was seen in all cases. Trabecular and subendothelial polymorphic infiltration was present to a variable extent in all cases. Study of the red pulp disclosed sinusoidal and Billroth cord infiltration by polymorphic large lymphocytes, including scattered large mononuclear cells with a prominent nucleolus. Activated lymphocytes exhibited a wide range of cell sizes and shapes but did not form aggregates. In all cases, large activated lymphocytes were admixed with small lymphocytes, plasma cells, and numerous macrophages. Characteristic Reed-Sternberg binucleate cells were not seen, but mononuclear and multinucleate pleomorphic cells were found in every case. Scattered macrophages with cytoplasmic nuclear fragments were seen throughout the red pulp, in some cases with phagocyted RBCs. Prominent germinal centers were not seen in any case, although reactive follicles contained some residual germinal centers Image 1.

Image 1.

Image 1 Red pulp expansion (A), with striking subendothelial infiltration (B), by a polymorphic background rich in large pleomorphic cells, macrophages, plasma cells, and small lymphocytes (C-D).

Immunohistochemical study revealed a majority of cytotoxic T lymphocytes, positive for CD3, CD2, CD5, CD8, and cytotoxic granules (TIA1, granzyme B, perforin) Image 2, Image 3, and Table 3. Scattered CD30-positive large lymphocytes were found in the red pulp. Large transformed cells showed either B-cell (CD20) or T-cell (CD3) markers. Immunoblasts and large activated lymphocytes were mostly positive for MUM1, were negative for BCL-6 and CD10, and showed weak BCL2 staining. Epstein-Barr virus (EBV)-encoded small RNA (EBER)-positive cells were seen mainly in the red pulp, homogeneously distributed. EBV/latent membrane protein 1 (LMP1) immunostaining showed isolated rare positive cells in all cases. Staining for κ and λ showed cytoplasmic staining by some of the activated B cells, without light chain restriction.

Image 2.

Immunohistochemical study disclosed numerous CD163-positive macrophages (A), a rich CD3-positive T-cell infiltrate (B), with a striking presence of scattered large B cells (case 2) (C) and CD8-positive T cells (D).

Image 3.

Some of the most striking findings emerge from the immunohistochemical study. A, T-cell infiltrate is mostly composed of cytotoxic T cells (x200). B, Scattered large lymphocytes positive for CD30 (x200). C, Endothelial cells may show intense active caspase 3 staining (x200). D, EBER staining present in scattered cells (case 3) (x400).

Active caspase 3 staining revealed strong staining in the nuclei of endothelial cells in scattered vessels (Image 3).

Differential diagnosis with Hodgkin lymphoma and diffuse large B-cell lymphoma was also considered necessary. Polymorphic histology and the presence of Sternbergoid cells forced us to consider the possibility of Hodgkin lymphoma, but the lack of a small lymphocyte background and the absence of a classic Hodgkin lymphoma immunophenotype (CD30+, CD15+, PAX5+, EBV/LMP) argued against this diagnosis. A possible diagnosis of diffuse large B-cell lymphoma was also considered in all cases, but polymorphic histology, the presence of activated T cells, and scattered apoptosis were strongly considered evidence against such a possibility.

Molecular Studies

Clonality analysis revealed TCR clonal patterns in four of the six cases evaluated. Clonal T-cell populations were detected in every positive case in a single gene locus (isolated TCR rearrangements) Figure 1. Three of six cases showed complete TCR G/B gene rearrangements (two G-B and one B-B). One case showed incomplete TCR rearrangements (B-C). The pattern of TCR rearrangements was polyclonal or nonclonal in the other two cases. IgH clonality analysis identified polyclonal B-cell populations in all six available cases.

Figure 1.

A, Case 3. GeneScan plots of T-cell receptor (TCR) BC and TCR GA tubes are shown. A single peak (200 base pairs [bp]) in a polyclonal background is found in TCRB tube C (Db-Jb) and a oligoclonal pattern is found in TCRG tube A (Vg-Jg). The other tubes (TCR-GB, TCR-BA, TCR-BB) showed a polyclonal pattern. B, Case 4. GeneScan plots of TCR GB (Vg-Jg) tube are shown. A clonal pattern with two dominant peaks is found (100, 166 bp). The other tubes (TCR-GA, TCR-BA, TCR-BB, TCR-BC) showed a polyclonal pattern (not shown). C, Case 5. GeneScan plots of TCR BB (Vg-Jg) are shown. A single clonal peak (268 bp) is found. The other tubes (TCR-GA, TCR-GB, TCR-BA, TCR-BC) showed a polyclonal pattern (not shown). D, Case 6. GeneScan plots of TCR GB (Vg-Jg) are shown. A clonal pattern (two peaks; 110, 166 bp) is found. The other tubes (TCR-GA, TCR-BA, TCR-BB, TCR-BC) showed a polyclonal pattern (not shown).

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