Case 4 -

Infectious Mononucleosis Paul E. Wakely, Jr.

Clinical History A 17 y/o young man presents with a 1.5 cm. right posterior cervical lymph node of unknown duration. He complains of an upper respiratory infection, and a slight fever. Cytopathology: Case 4 - Figure 1 - Case 4 - Figure 2 - Case 4 - Figure 3 - hypercellular smears with a range of lymphocytes an abnormally high percentage of immunoblasts, and a lesser number of centroblasts immunoblasts: enlarged nuclei, usually one nucleolus, a moderate amount of cytoplasm which in the Diff-Quik stain has a deeply basophilic peripheral border plasmacytoid lymphocytes and rare binucleated cells were also present; there were no FC fragments. Diagnosis: Infectious Mononucleosis Discussion Table 26. Infectious Mononucleosis(IM), clinical features: a virally induced (Epstein-Barr virus) disorder spread from person-to-person contact that primarily affects adolescents and young adults; a wide age range self-limited, 3-4 weeks adolescents, young adults typical clinical: fever, malaise, pharyngitis, lymphadenopathy (typically cervical, but axillary and inguinal also). lymph nodes often tender to palpation, and movable splenomegaly is common; splenic rupture secondary to trauma possible laboratory findings: peripheral blood atypical lymphocytosis, positive monospot (heterophil) test EBV stimulates a polyclonal B-cell proliferation which in turn stimulates a killer T-cell response. IM is thus a combined clinical-serologic diagnosis. IM is one of several EBV induced diseases: Table 27. EBV Positive T-Cell Disorders • Infectious Mononucleosis • Angioimmunoblastic T-Cell Lymphoma • B cell In Peripheral T-Cell Lymphoma • Aggressive NK-Cell Lymphoma • Extra-nodal NK/T-Cell Lymphoma • Enteropathy-type T-Cell Lymphoma • Plasmablastic Lymphoma   Role of FNA is to suggest or exclude this diagnosis in a patient who has either not undergone serologic testing, or whose serology is negative thus attempting to avoid an excisional biopsy when it may be unnecessary. Occasionally FNA is also used to exclude, or diagnose a malignant lymphoma in a patient with IM-like clinical symptoms. Aspiration smears are hypercellular with a polymorphous lymphoid population characterized by an increased percentage of immunoblasts, centroblasts, plasmacytoid lymphocytes, and occasionally increased plasma cells. Immunoblasts are large cells with fine nuclear chromatin, 1-3 prominent nucleoli, and ample peripherally basophilic cytoplasm. Pleomorphic binucleated immunoblasts simulating R-S cells are rare in aspirates. These cells are CD15 negative, but can be CD30 positive. Differential diagnosis: RLH Hodgkin's Lymphoma large cell non-Hodgkin lymphoma Kikuchi's disease Distinguishing aspirate of IM from RLH: recognize the increase of immunoblasts and plasmacytoid lymphocytes coupled with the clinical picture. Unlike RLH, TBMs and FC fragments are only a minor component of the IM smear, if present at all. Nonetheless, very early in the course of IM lymphadenopathy may only demonstrate a florid RLH without the large population of transformed cells, and IM can be indistinguishable from an early phase reactive lymph node. Other causes of immunoblast proliferation: as anti-convulsant lymphadenopathy, Herpes simplex lymphadenitis, and drug hypersensitivity - may be indistinguishable from IM. Clinical and serologic data combined with the cytopathology is therefore necessary to make a specific diagnosis. IBs and large lymphocytes of IM may be misinterpreted as large cell lymphoma. Distinct from a lymphoma, however, a range of lymphoid cells still exists in IM even if immunoblasts predominate. Immunophenotyping is helpful, and shows B-cell polyclonality with a suppressor/cytotoxic T-cell phenotype in IM, unlike the monclonality of large cell lymphoma – most of which are B-cell type. Kikuchi's lymphadenitis (Kikuchi-Fujimoto disease) self-limited lymphadenopathy of unknown cause characterized by an abnormal proliferation of immunoblasts uncommon in North America in contrast to its prevalence in Oriental women lymphadenopathy (either single or multiple) principally affects cervical lymph nodes patients may have fever, lymph node tenderness, atypical lymphocytosis of the peripheral blood similar to IM Kikuchi's has been mistaken histologically for large cell lymphoma on occasion because the high percentage of immunoblasts. increased IBs, monocytoid lymphocytes a "dirty" background due to an abundance of cellular debris and karyorrhexis in this lymphadenopathy absence of neutrophils key feature: presence of phagocytic histiocytes with crescent-shaped, sometimes twisted nuclear contours that occasionally have a sharply angulated edge. These histiocytes are large, rounded, and had abundant cytoplasm that was distended with phagocytosed granular and nuclear debris similar to the diathesis found in the smear background. Conventional TBMs have oval/spherical nuclei without the crescentic configuration. It is important to note that neutrophils are absent in Kikuchi's disease -unlike cat-scratch disease. References for All Cases